Serum human chorionic gonadotropin levels throughout normal pregnancy GLENN JOAN
D. RASOR,
DONALD HAL
BRAUNSTEIN, M.A.
ADLER, DANZER,
MACLYN
M.D. M.D.
E.
Los Angeles,
M.D.
WADE,
M.D.
California
chorionic gonadotropin (hCG) 1evel.smere measured in the sera of 443 pregnant women by the beta-hCG radioimmunoassay in order to determine zf the third-trimester secondary peak in hCG levels observed by less specz$c immunoassays was due to cross-reacting substances. hCG was detected as early as six days after presumed conception and peaked between 56 and 68 days, with a nadir at 18 weeks. No secondary rice in hCG levels was demonstrated, indicating that the nonspec$c hCG immunoassays give spuriously high values for hCG during the last trimester qf pregnancy. (AM. J. OBSTET. GYNECOL. 126: 678, 1976.) Human
I N 1938, BOYCOTT and Rowlands’ first described the quantitative pattern in serum of human chorionic gonadotropin (hCG) secretion throughout normal pregnancy. Since then, numerous bioassays and immunologic methods have been utilized to measure hCG in the serum of pregnant women. The qualitative aspects of hCG secretion during the first two trimesters are remarkably similar between reports, with peak levels of hCG being found between 8 and 12 weeks after the last menstrual period. However, the hCG secretory pattern during the last trimester has varied according to the method used for measuring ;he molecule. Bioassays generally show a persistently low level of hCG in the serum that does not differ significantly from those found in the latter part of the second trimester,‘while immunoassay techniques have usually demonstrated a secondary rise in hCG during
the last trimester.3* -I These discrepancies may reflect the presence of immunologically active, but biologically inactive, fragments or subunits of hCG or cross-reaction with other glycoprotein hormones. In order to better define the qualitative and quantitative aspects of hCG secretion, we have examined the hCG content of sera from 443 women with uncomplicated pregnancies by using a radioimmunoassay for hCG which does not significantly cross react with the other glycoprotein hormones or their alpha subunits.
Materiel and methods Specimens. Samples of 7 ml. of blood were obtained from 443 women with normal, uncomplicated pregnancies by venipuncture. The serum was rapidly separated from the clot and frozen at -20” C. until use. Dating of the serum sample was accomplished by utilizing the first day of the last menstrual period as Day 1 of pregnancy. When such information was not available, dating of the specimen was based upon the date of delivery of a normal term infant, with the assumption that the period of gestation was 40 weeks. hCG measurements. The double-antibody beta radioimmunoassay (RIA) for hCG previously described by Vaitukaitis and associates5 was utilized to measure hCG in the serum samples. In this assay an antisera generated against the beta subunit of hCG is used. It is specific for hCG and its beta subunit in the presence of physiologic amounts of human luteinizing
From the Departments of Medicine and Obstetrics and Gynecology, Cedars-Sinai Medical Center, and the University of California Los Angeles School of Medicine. Supported in part b United Grant 5-SO1 RR05468. Receivrd
for publication
Rev&d
March
Accepted April
States Public
October
Health
Service
14, 1975.
15, 1976. 9, 1976.
Reprint requests: Qr. Glenn D. Braunrtein, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, California 90048.
678
Serum
hormone (hLH).’ There is no significant cross-reaction with the alpha subunit of hCG (0.4 per cent) or with the other glycoprotein hormones. The original RIA has been modified in that lz51-hCG rather than ‘251-hCGbeta subunit is utilized for tracer purposes without a change in the assay’s sensitivity or specificity. A highly purified preparation of hCG (CR 115, 5,000 I.U. per milligram by radioimmunoassay relative to the Second International Standard for hCG) was used as the standard. hLH/hCG measurements. An antiserum raised against hLH which does not discriminate between hLH and hCG was supplied by the Hormone Distribution Officer, National Institute of Arthritis, Metabolism, and Digestive Diseases. It was utilized in a doubleantibody RIA with lZ51-hCG used as a trace and a purified preparation of hCG (CR 115) used as the standard. The alpha subunit of hCG cross reacts with intact hCG approximately 1 per cent in this assay, while hLH cross reacts 100 per cent.* Results were expressed in terms of International Units per milliliter, relative to the Second International Standard for hCG. Statistical analyses. The statistical methods of Rodbard and Frazier’ were used to evaluate each RIA. The differences between correlated means were compared by Student’s t test. A least-squares linear regression analysis between the hCG levels obtained from the beta-subunit RIA and those obtained from the same samples by the nonspecific hLH/hCG RIA was carried out on ;I Compucorp calculator, Model 145-E Statistician.
Results The mean values for hCG from the third week after the last menstrual period through parturition are shown in Table I and Fig. 1. hCG was detected as early as six days after presumed ovulation (Day 14) with peak levels being reached at 8 to 8.5 weeks. The concentration dropped rapidly after 11% weeks, reached a nadir at 18 weeks, and remained low throughout the rest of gestation. No significant difference in mean concentration was detected between sequential weeks from I8 to 40 weeks of gestation. Even when the values between 18 and 26% weeks were grouped and compared to those between 27 and 40 weeks, no significant difference was found (P < 0.4). A highly significant linear correlation was found between the hCG concentration in 33 samples of pregnancy sera determined by both the beta-subunit RIA and the less-specific hLH/hCG RIA (r = 0.94; p < 0.001). However, the levels of hCG measured were *Braunstein,
G. D.: Unpublished
observations.
HCG
during
normal
pregnancy
679
Table I. Mean serum hCG levels throughout normal gestation as determined by the beta-hCG RI.1 ggstational dates are based on the first d,!\ of the last menstrual period (LMP). No. = Number of patients in each group
3-3.5 4-4.5 5-5.5 6-6.5 7-7.5 U-8.5 9-9.5 10-10.5 11-11.5 12-12.5 13-13.5 14-14.5 15-15.5 16-16.5 17-17.5 18-18.5 19-19.5 20-20.5 21-21.5 22-22.5 23-23.5 24-24.5 25-25.5 26-26.5 27-27.5 28-28.5 29-29.5 30-30.5 31-31.5 32-32.5 33-33.5 34-34.5 35-35.5 36-36.5 37-37.5 38-38.5 39-39.5 40-40.5
11 1X 19 12 6 6 3 9 12 18 9 14 17 8 14 17 12 9 13 8 9 15 14 14 18 9 7 10 7 I3 12 11 17 ii 15 19 4
0.02 16 (I.353 2.27 ti.fi.4 13.61 46.X3 44.71 37.75 38.36 28.48 30.73 24.76 19.01 16.81 15.26 10.01 11.05 9.06 10.66 10.10 5.x9 9.x.5 9.48 .5.4x 8.15 14.94 7.56 7.,40 12.07 12.10 1 1 ..5 2 X.65 12.00 7.24 6.16 I 1.89 10.1)2 .~.30
0.0057 0.089 0.39 .I.16 2.74 4.71 3.69 5.42 8.10 3.64 2.x4 3.7.5 1.57 2.79 2.55 1.20 1.99 1.0x 2.09 2.47 0.88 I .32 I .TO 0.97 1.83 c4.01 2.37 1 .Y3 3.41 4.12 2.64 I .89 2.67 1.38 1.4 1 1.79 1.0x 3.13
consistently greater by the hLH/hCG RIA than by the beta-subunit assay. A comparison of the separate linear regression analyses for the hCG levels in the first and second trimesters versus the third trimester revealed a steeper slope during the third trimester. This configuration indicated that relative to the beta-subunit RIA the hLH/hCG RIA measured more immunoreactive material in the thrid trimester than in the first two trimesters.
Comment hCG is a glycoprotein hormone composed of two dissimilar subunits, the alpha and beta subunits.7 The alpha subunit of hCG is virtually identical to the alpha subunit of hLH physiochemically, structurally, and
680
Braunstein et al.
50 45 40 35 30 25 20 15 10 5 0
4
0
12 WEEKS
16 AFTER
20 LAST
24 MENSTRUAL
28
32
immunologically, while the beta subunit of hCG differs from the beta subunit of hLH in that the beta subunit of hCG contains 30 amino acid residues in excess of that found in the beta subunit of hLH.* Because of the close homology between these two molecular species, antisera generated against either intact hCG or intact hLH would be expected to demonstrate immunologic cross-reactivity between these two molecules, an observation which has been repeatedly confirmed.’ It was with this in mind that an RIA was developed which utilized the purified beta subunit of hCG for antigenic purposes. The antisera directed against the beta subunit of hCG did not show significant cross-reaction with physiologic concentrations of intact hLHS or with the alpha subunit of hCG.‘O The secretion of hCG during normal pregnancies has been studied for many years. The reports in which hCG was measured by bioassay methods are remarkably similar qualitatively. ‘* ’ By these methods, hCG is generally detected as early as 24 days after the last menstrual period. Peak levels of serum hCG are reached between the eighth and twelfth weeks of gestation. Thereafter, the levels decline, reaching a nadir in the second trimester where they remain until parturition. Initial immunoassay methods for measuring hCG utilized hemagglutination-inhibition or complementfixation techniques. 3, ‘I In the last ten years, a number of radioimmunoassays have been used to determine serum levels of hCG.’ All these immunologic methods were hampered by the above-noted cross-reaction between hCG and hLH, since the immunogen used was intact hCG or hLH. The majority of these immunoassays were quite similar quantitatively, with peak levels of hCG again having been detected between 8 and 12
40
PERIOD
1. Mean serum hCG levels throughout normal pregnancy. Arithmetical Bars represent f 1 standard error of the mean
Fig.
36
scale used on ordinate.
weeks, followed by a rapid decline to low levels during the second trimester. The immunologic methods differed from the bioassay results in that a secondary p@ak of hCG was detected during the third trimester by the immunoassays. The discrepancy could be explained by the secretion late in pregnancy of an immunologically active, but biologically inactive, form of hCG, the concomitant overproduction of the biologically inactive free alpha and/or beta subunits of hCG, or by the presence in the blood of significant levels of other cross-reacting glycoproteins. There exists a great deal of evidence that hCG secreted during pregnancy is, indeed, heterogeneous. Vaitukaitis” has demonstrated that a “big” hCG is present in placental extracts, along with the immunoreactive forms that are usually found in the serum and urine. Other investigators have shown heterogeneity in the molecular composition of the hCG found in urine during pregnancy, due to differences in the content of sialic acid.‘” Progressive removal of the sialic acid moiety from hCG leads to a marked reduction of the biological activity with maintenance of the immunoreactivity.” Since hCG containing no sialic acid is immunologically active in the beta-hCG KIA, the lack of a third-trimester secondary rise in hCG levels, when measured by this assay, suggests that excessive secretion of biologically inactive, partially sialyated forms of hCG does not occur. Studies by Vaitukaitis” on placental extracts and Franchimont and co-workers” on placental organ cultures, have shown that the normal human placenta contains and secretes large amounts of the free alpha subunit of hCG with little or no concomitant storage or secretion of the free beta subunit. Ashitaka and associ-
Serum
ates’”
have
creasing
demonstrated amounts
progresses, unit ever,
while
of’ hCG the only
the
nonspecificbeta
that
We are itative
also
thus
unable
differences nonspecific
pregnancy
that
immunoassays
of the
assay. pregnancy,
of
this
hormone
are
rise in immunoreac-
this
be expected explain
pattern are
that
the
substance. of found are
used
the
qual-
hCG
secretion
when
bioassays
to measure
the level in
nonspecific
hCG
substances
together hLH/hCG
of hCG the
secretion to that with
tielermined
b)
by bioas-
observation
at-c tar
10 those
ir&catc< rne‘lsuring
thoughouc
values
that overesti-
in corrjpitrison RI A.
to hCG
681
c-onsislc-ntly
immunoassays high
pregnancy
ob~..~i~led the
RI.4 in serum
in addition last
normai
beta-hCG
in spuriouslv the
during
of hCG is similar
finding, specific
obtained
during
pattern RIA
‘I-his
resulting
concerning
it would
the
trimcs-
throughout
‘The
less
mates in
is available
to satisfactorily in
last
says. the
indicate
cross-reaction
levels
detect
sub-
measured
the
in this
third-trimester since
could
throughout
by the
serum
elevated
the
during
hormone. the beta-hCG
How-
co-workersI
of hCG
in-
beta
gestation.
of the hCG
information
activity,
bioassays
fbr
secretes as pregnancy
of the free
and RIA
in maternal for
hCG
levels
milliliter
subunits
no
levels
responsible
and
Ashitaka per
be accounted and
it is unlikely rive
from
placenta
subunits
throughout
hLH/hCG
Although hLH
serum low
0.4 1.L’.
ter could alpha
the
the
alpha
remain
data
that
that
of free
HCG
that orhe
pregnancy. !I( : among the human glycoprotein hormones and their subunits, in Saxena. B., Gandy, H., and Beiing. C., editors: New York, John Wiley & Sons, Inc., 1972. pp. 435-443. 11. Mishell, D. J., Jr,, Wide, L.. and Gem-/.& (1. A.: Immunologic determination of human chorionic gonadotropin in serum, J. Clin. Endorrinol. bhatab. 23: 125, 1963. 12. Vaitukaitis. J. L.: Changing placental concentrations of human chorionic gonadotropin and its subunits during gestation, J. Clin. Endocrinol. Metab. 38: 255, 1974. 13. Van Hell, H.. Goverde, B. C., Schuurs. A. H. W. ?vl.. DeJager, E., Matthijsen, R., and Homan, J. D. H.: Purification, characterization and immunoc,hemical properties of human chorionic gonadotropin. Sature 212: 261, 1966. 14. Van Hall, E. V., Vaitukaitis, J. L., Ross, G. ‘1.) Hickman, J. W.. and Ashwell, G.: Immunologic and biologic activity of hCG following progressive desialvlation. Endocrinolog! 88: 456, 1971. 15. Franchimont, P., Gaspard, U., Renter. .i.. and Heynen, G.: Polymorphism of protein and polvpeptide hormones, Clin. Endocrinol. 1: 315, 1972. 16. Ashitaka. Y., Nishimura, R., Futamura. k.. Ohashi, $4.. and Tojo, S.: Serum and chorionic tissue concentrations of human chorionic gonadotropin and its subunits during pregnancy. Endocrinol. Jap. 21: 547. 197 i.
D. RASOR,
DONALD HAL
BRAUNSTEIN, M.A.
ADLER, DANZER,
MACLYN
M.D. M.D.
E.
Los Angeles,
M.D.
WADE,
M.D.
California
chorionic gonadotropin (hCG) 1evel.smere measured in the sera of 443 pregnant women by the beta-hCG radioimmunoassay in order to determine zf the third-trimester secondary peak in hCG levels observed by less specz$c immunoassays was due to cross-reacting substances. hCG was detected as early as six days after presumed conception and peaked between 56 and 68 days, with a nadir at 18 weeks. No secondary rice in hCG levels was demonstrated, indicating that the nonspec$c hCG immunoassays give spuriously high values for hCG during the last trimester qf pregnancy. (AM. J. OBSTET. GYNECOL. 126: 678, 1976.) Human
I N 1938, BOYCOTT and Rowlands’ first described the quantitative pattern in serum of human chorionic gonadotropin (hCG) secretion throughout normal pregnancy. Since then, numerous bioassays and immunologic methods have been utilized to measure hCG in the serum of pregnant women. The qualitative aspects of hCG secretion during the first two trimesters are remarkably similar between reports, with peak levels of hCG being found between 8 and 12 weeks after the last menstrual period. However, the hCG secretory pattern during the last trimester has varied according to the method used for measuring ;he molecule. Bioassays generally show a persistently low level of hCG in the serum that does not differ significantly from those found in the latter part of the second trimester,‘while immunoassay techniques have usually demonstrated a secondary rise in hCG during
the last trimester.3* -I These discrepancies may reflect the presence of immunologically active, but biologically inactive, fragments or subunits of hCG or cross-reaction with other glycoprotein hormones. In order to better define the qualitative and quantitative aspects of hCG secretion, we have examined the hCG content of sera from 443 women with uncomplicated pregnancies by using a radioimmunoassay for hCG which does not significantly cross react with the other glycoprotein hormones or their alpha subunits.
Materiel and methods Specimens. Samples of 7 ml. of blood were obtained from 443 women with normal, uncomplicated pregnancies by venipuncture. The serum was rapidly separated from the clot and frozen at -20” C. until use. Dating of the serum sample was accomplished by utilizing the first day of the last menstrual period as Day 1 of pregnancy. When such information was not available, dating of the specimen was based upon the date of delivery of a normal term infant, with the assumption that the period of gestation was 40 weeks. hCG measurements. The double-antibody beta radioimmunoassay (RIA) for hCG previously described by Vaitukaitis and associates5 was utilized to measure hCG in the serum samples. In this assay an antisera generated against the beta subunit of hCG is used. It is specific for hCG and its beta subunit in the presence of physiologic amounts of human luteinizing
From the Departments of Medicine and Obstetrics and Gynecology, Cedars-Sinai Medical Center, and the University of California Los Angeles School of Medicine. Supported in part b United Grant 5-SO1 RR05468. Receivrd
for publication
Rev&d
March
Accepted April
States Public
October
Health
Service
14, 1975.
15, 1976. 9, 1976.
Reprint requests: Qr. Glenn D. Braunrtein, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, California 90048.
678
Serum
hormone (hLH).’ There is no significant cross-reaction with the alpha subunit of hCG (0.4 per cent) or with the other glycoprotein hormones. The original RIA has been modified in that lz51-hCG rather than ‘251-hCGbeta subunit is utilized for tracer purposes without a change in the assay’s sensitivity or specificity. A highly purified preparation of hCG (CR 115, 5,000 I.U. per milligram by radioimmunoassay relative to the Second International Standard for hCG) was used as the standard. hLH/hCG measurements. An antiserum raised against hLH which does not discriminate between hLH and hCG was supplied by the Hormone Distribution Officer, National Institute of Arthritis, Metabolism, and Digestive Diseases. It was utilized in a doubleantibody RIA with lZ51-hCG used as a trace and a purified preparation of hCG (CR 115) used as the standard. The alpha subunit of hCG cross reacts with intact hCG approximately 1 per cent in this assay, while hLH cross reacts 100 per cent.* Results were expressed in terms of International Units per milliliter, relative to the Second International Standard for hCG. Statistical analyses. The statistical methods of Rodbard and Frazier’ were used to evaluate each RIA. The differences between correlated means were compared by Student’s t test. A least-squares linear regression analysis between the hCG levels obtained from the beta-subunit RIA and those obtained from the same samples by the nonspecific hLH/hCG RIA was carried out on ;I Compucorp calculator, Model 145-E Statistician.
Results The mean values for hCG from the third week after the last menstrual period through parturition are shown in Table I and Fig. 1. hCG was detected as early as six days after presumed ovulation (Day 14) with peak levels being reached at 8 to 8.5 weeks. The concentration dropped rapidly after 11% weeks, reached a nadir at 18 weeks, and remained low throughout the rest of gestation. No significant difference in mean concentration was detected between sequential weeks from I8 to 40 weeks of gestation. Even when the values between 18 and 26% weeks were grouped and compared to those between 27 and 40 weeks, no significant difference was found (P < 0.4). A highly significant linear correlation was found between the hCG concentration in 33 samples of pregnancy sera determined by both the beta-subunit RIA and the less-specific hLH/hCG RIA (r = 0.94; p < 0.001). However, the levels of hCG measured were *Braunstein,
G. D.: Unpublished
observations.
HCG
during
normal
pregnancy
679
Table I. Mean serum hCG levels throughout normal gestation as determined by the beta-hCG RI.1 ggstational dates are based on the first d,!\ of the last menstrual period (LMP). No. = Number of patients in each group
3-3.5 4-4.5 5-5.5 6-6.5 7-7.5 U-8.5 9-9.5 10-10.5 11-11.5 12-12.5 13-13.5 14-14.5 15-15.5 16-16.5 17-17.5 18-18.5 19-19.5 20-20.5 21-21.5 22-22.5 23-23.5 24-24.5 25-25.5 26-26.5 27-27.5 28-28.5 29-29.5 30-30.5 31-31.5 32-32.5 33-33.5 34-34.5 35-35.5 36-36.5 37-37.5 38-38.5 39-39.5 40-40.5
11 1X 19 12 6 6 3 9 12 18 9 14 17 8 14 17 12 9 13 8 9 15 14 14 18 9 7 10 7 I3 12 11 17 ii 15 19 4
0.02 16 (I.353 2.27 ti.fi.4 13.61 46.X3 44.71 37.75 38.36 28.48 30.73 24.76 19.01 16.81 15.26 10.01 11.05 9.06 10.66 10.10 5.x9 9.x.5 9.48 .5.4x 8.15 14.94 7.56 7.,40 12.07 12.10 1 1 ..5 2 X.65 12.00 7.24 6.16 I 1.89 10.1)2 .~.30
0.0057 0.089 0.39 .I.16 2.74 4.71 3.69 5.42 8.10 3.64 2.x4 3.7.5 1.57 2.79 2.55 1.20 1.99 1.0x 2.09 2.47 0.88 I .32 I .TO 0.97 1.83 c4.01 2.37 1 .Y3 3.41 4.12 2.64 I .89 2.67 1.38 1.4 1 1.79 1.0x 3.13
consistently greater by the hLH/hCG RIA than by the beta-subunit assay. A comparison of the separate linear regression analyses for the hCG levels in the first and second trimesters versus the third trimester revealed a steeper slope during the third trimester. This configuration indicated that relative to the beta-subunit RIA the hLH/hCG RIA measured more immunoreactive material in the thrid trimester than in the first two trimesters.
Comment hCG is a glycoprotein hormone composed of two dissimilar subunits, the alpha and beta subunits.7 The alpha subunit of hCG is virtually identical to the alpha subunit of hLH physiochemically, structurally, and
680
Braunstein et al.
50 45 40 35 30 25 20 15 10 5 0
4
0
12 WEEKS
16 AFTER
20 LAST
24 MENSTRUAL
28
32
immunologically, while the beta subunit of hCG differs from the beta subunit of hLH in that the beta subunit of hCG contains 30 amino acid residues in excess of that found in the beta subunit of hLH.* Because of the close homology between these two molecular species, antisera generated against either intact hCG or intact hLH would be expected to demonstrate immunologic cross-reactivity between these two molecules, an observation which has been repeatedly confirmed.’ It was with this in mind that an RIA was developed which utilized the purified beta subunit of hCG for antigenic purposes. The antisera directed against the beta subunit of hCG did not show significant cross-reaction with physiologic concentrations of intact hLHS or with the alpha subunit of hCG.‘O The secretion of hCG during normal pregnancies has been studied for many years. The reports in which hCG was measured by bioassay methods are remarkably similar qualitatively. ‘* ’ By these methods, hCG is generally detected as early as 24 days after the last menstrual period. Peak levels of serum hCG are reached between the eighth and twelfth weeks of gestation. Thereafter, the levels decline, reaching a nadir in the second trimester where they remain until parturition. Initial immunoassay methods for measuring hCG utilized hemagglutination-inhibition or complementfixation techniques. 3, ‘I In the last ten years, a number of radioimmunoassays have been used to determine serum levels of hCG.’ All these immunologic methods were hampered by the above-noted cross-reaction between hCG and hLH, since the immunogen used was intact hCG or hLH. The majority of these immunoassays were quite similar quantitatively, with peak levels of hCG again having been detected between 8 and 12
40
PERIOD
1. Mean serum hCG levels throughout normal pregnancy. Arithmetical Bars represent f 1 standard error of the mean
Fig.
36
scale used on ordinate.
weeks, followed by a rapid decline to low levels during the second trimester. The immunologic methods differed from the bioassay results in that a secondary p@ak of hCG was detected during the third trimester by the immunoassays. The discrepancy could be explained by the secretion late in pregnancy of an immunologically active, but biologically inactive, form of hCG, the concomitant overproduction of the biologically inactive free alpha and/or beta subunits of hCG, or by the presence in the blood of significant levels of other cross-reacting glycoproteins. There exists a great deal of evidence that hCG secreted during pregnancy is, indeed, heterogeneous. Vaitukaitis” has demonstrated that a “big” hCG is present in placental extracts, along with the immunoreactive forms that are usually found in the serum and urine. Other investigators have shown heterogeneity in the molecular composition of the hCG found in urine during pregnancy, due to differences in the content of sialic acid.‘” Progressive removal of the sialic acid moiety from hCG leads to a marked reduction of the biological activity with maintenance of the immunoreactivity.” Since hCG containing no sialic acid is immunologically active in the beta-hCG KIA, the lack of a third-trimester secondary rise in hCG levels, when measured by this assay, suggests that excessive secretion of biologically inactive, partially sialyated forms of hCG does not occur. Studies by Vaitukaitis” on placental extracts and Franchimont and co-workers” on placental organ cultures, have shown that the normal human placenta contains and secretes large amounts of the free alpha subunit of hCG with little or no concomitant storage or secretion of the free beta subunit. Ashitaka and associ-
Serum
ates’”
have
creasing
demonstrated amounts
progresses, unit ever,
while
of’ hCG the only
the
nonspecificbeta
that
We are itative
also
thus
unable
differences nonspecific
pregnancy
that
immunoassays
of the
assay. pregnancy,
of
this
hormone
are
rise in immunoreac-
this
be expected explain
pattern are
that
the
substance. of found are
used
the
qual-
hCG
secretion
when
bioassays
to measure
the level in
nonspecific
hCG
substances
together hLH/hCG
of hCG the
secretion to that with
tielermined
b)
by bioas-
observation
at-c tar
10 those
ir&catc< rne‘lsuring
thoughouc
values
that overesti-
in corrjpitrison RI A.
to hCG
681
c-onsislc-ntly
immunoassays high
pregnancy
ob~..~i~led the
RI.4 in serum
in addition last
normai
beta-hCG
in spuriouslv the
during
of hCG is similar
finding, specific
obtained
during
pattern RIA
‘I-his
resulting
concerning
it would
the
trimcs-
throughout
‘The
less
mates in
is available
to satisfactorily in
last
says. the
indicate
cross-reaction
levels
detect
sub-
measured
the
in this
third-trimester since
could
throughout
by the
serum
elevated
the
during
hormone. the beta-hCG
How-
co-workersI
of hCG
in-
beta
gestation.
of the hCG
information
activity,
bioassays
fbr
secretes as pregnancy
of the free
and RIA
in maternal for
hCG
levels
milliliter
subunits
no
levels
responsible
and
Ashitaka per
be accounted and
it is unlikely rive
from
placenta
subunits
throughout
hLH/hCG
Although hLH
serum low
0.4 1.L’.
ter could alpha
the
the
alpha
remain
data
that
that
of free
HCG
that orhe
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