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Human placental lactogen, estradiol-17β, and progesterone levels in the third trimester and their respective values for detecting twin pregnancy
Human placental lactogen, estradiol-17 {3, and progesterone levels in the third trimester and their respective values for detecting twin pregnancy S. BATRA. PH.D. N. 0. SJOBERG, PH.D., M.D. A. ABERG, M.D. Lund, Sweden Plasma levels of HPL, P, and E2 was serially measured between weeks 30 to 36 in simplex and duplex pregnancies. Levels of both HPL and P were significantly higher in duplex than in simplex pregnancies. However, this was not the case for E2. There was a significant correlation between HPL and P levels. It is indicated that measurement of plasma P levels, as those of HPL levels, but not E2 levels is of value for detecting twin pregnancy. (AM.
J.
131: 69, 1978.)
0BSTET. GYNECOL.
LEvELS oF human placental lactogen (HPL), as well as of ' ' ------ nl::!ct>ntal hormones such as estradiol-17 8 IE2) -- otht>r and progesterone (P), increase with advancing pregnancy.1 Due to the fact that the HPL level is significantly higher in multibirth pregnancy, 2- 8 it can be, as demonstrated recently, used as a screening test for detecting twin pregnancy. 9 Although the levels of both E2 and P, since they are also placental hormones, would be expected to be higher in multibirth pregnancy, only fragmentary data are available on this point. In fact, we are not aware of any study in which the levels of both E2 and P in twin pregnancies have been measured. Besides the fact that this kind of information in itself would be of general interest it could also prove to be of clinical aid for detecting twin pregnancy. In the present study we have compared the levels of HPL, E2, and Pin simplex pregnancies during the third trimester with those in duplex. ~-----
-----
-
-
--
-
-
-
-
-
.
From the Department of Obstetrics and Gynecology, University Hospital Lund. Supported by the Ford Foundation. Receivedfor publication April 26, 1977. Revised September 13, 1977. Accepted October I, 1977. Reprint requests: Dr. Nils-Otto Sjoberg, Department of Obstetrics and Gynecology, University Hospital, S-221 85 Lund, Sweden. 0002~9378/78/01131-0069$00.40/0
©
1978 The C. V. _r..{osby Co.
Materials and methods Blood samples were obtained seriallv from 56 women (21 to 38 years of age) between weeks 30 to 36 of pregnancy. Fifteen women were delivered of simplex and 41 of twins. HPL was estimated in the plasma by a radioimmunoassay performed according to the method described by Letchworth
Results The levels of HPL in simplex and duplex pregnancies from weeks 30 to 36 are shown in Fig. 1. In duplex pregnancies the levels of HPL were significantly higher (p < 0.005) for each week than the respective levels for simplex. Similarly, the plasma P concentration was significantly higher in duplex than in simplex pregnancies (Fig. 2). The mean levels of HPL and Pin duplex pregnancy for each week (30 to 36 weeks) were at least 60 per cent greater than in simplex. On the other hand, the levels of E2 did not show a significant difference between simplex and duplex pregnancies in any of the weeks studied (Fig. 3). Fig. 4 shows a plot of HPL and P values in all samples
69
May I, 1978
70 Batra, Sjoberg, and Aberg
Am.
J. Obstet. Gynecol.
401 Duplex 7.0
30
-"' E
Simplex
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30
31
32
33
34
35
36
Weeks of pregnancy
Fig. 3. Mean levels (±S.E.) of estradiol-17/3 in simplex and duplex pregnancies from weeks 30 to 36.
Weeks of pregnancy
Fig. 1. Mean levels (±S.E.) of HPL in simplex and duplex pregnancies from weeks 30 to 36.
3001 250
I
Comment
200
..§
Q;
(n = 91) from twin pregnancies, irrespective of gestational length. There was a highly significant correlation (p < 0.005) between the concentrations of HPL and P in plasma from twin pregnancies. The regression line of x on y (x = 14.84 y + 105.89) is aiso shown.
150
u;
t
so
30
31
33 34 35 32 Weeks of pregnancy
36
Fig. 2. Mean level (±S.E.) of progesterone in simplex and duplex pregnancies from weeks 30 to 36.
The levels of HPL as well as other hormones of placental origin would be expected to be higher in multibirth than in unibirth pregnancy. This has been shown for HPL, and due to a significant difference between simplex and duplex pregnancies the measurement of this hormone in plasma has been used as a screening test for detecting twin pregnancy. 9 The results of the present study show that measurements of P levels could also provide a satisfactory screening test, since the levels were significantiy higher in duplex than in simplex pregnancy. Since both HPL and P are produced in the same placental cells, namely syncytiotrophoblasts, it was not surprising to find a significant correlation (Fig. 4) between the levels of these two hormones. With the exception of one study/ such a correlation between HPL and P has been reported in simplex pregnancy. 14 · 15 The present finding, showing an insignificant difference in the levels of E2 between simplex and duplex pregnancy, is somewhat puzzling in view of the fact that this hormone is also produced in the syncytiotrophoblasts. There can be several possible explanations for this unexpected finding. There is now considerable evidence that the produc-
Volume !31 Number l
Placental hormones for detecting twin pregnancy
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121 11
71
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100
150
300
250
200
350
400
Progesterone ng I ml Fig. 4. Relationship between the levels of HPL and progesterone in twin pregnancy plasma (n = 91). The regression lines of both yon x (y = 0.0 lx + 4.85) and x on y (n == 14.84y + 105.89) are shown
tion of P by placenta is more or less independent of the fetus. 16 · 17 The production of E2 during pregnancy is, however, to a great extent dependent on the supply of precursors from the fetus. 16 • 17 Despite th.e presence of two fetuses, there may be a limiting step either in the availability of the E2 precursors from fetus to placenta or in the synthesis of E2 in the placenta from the presursors. Another explanation might be related to a
REFERENCES
J.,
and Benirschke, K.: Principles and Management of Human Reproduction, Philadelphia, London, Toronto, 1972, W. B. Saunders Company. 2. Josimovich, J. B.: Placental lactogenic hormone, in Fuchs, F., and Klopper, A., editors: Endocrinology of Pregnancy, New York, 1971, Harper & Row, p. 184. 3. Genazzani, A. R., Cocola, F.; Neri, P., and Fioretti, P.: Human chorionic somacomammotropin (HCS) levels in norma! and pathological pregnancies and their correlation with the placental function, Acta Endocrinol. 71 (Suppl.): 167, 1972. 4. Lebech, P. E.. and Borggaard, B.: Serum levels of human I. Reid, D. E., Ryan, K.
greater dependence of E2 than P on the fetus for its metabolism. There is evidence that urinary estriol excretion in the twin pregnancies is significantly greater than in simplex pregnancies. 18 The above ex~ planations, however, must remain speculative until a more precise information on the biosynthesis and metabolism of steroids in fetus and placenta is available.
chorionic somatomammotropin (HCS) in normal and abnormal pregnancies, Acta Endocrinol. 75 (Suppl.): 182. 1974. 5. Dawood, M. Y., and Ratnam, S. S.: Serum unconjugated estradiol-17 .B in normal pregnancy measured by radioimmunoassay, Obstet. Gynecol. 44: 194, 1974. 6. Dawood, M. Y.: Circulating maternal serum progesterone in high-risk pregnancies, AM. J. OsSTET. GYNECOI .. 125: 832, 1976. 7. Conly, P. W., Spellacy, W. M., and Claveland, W. W.: Maternal plasma progesterone and human placental lactogen in the last month of full-term pregnancy, Clin. Res. Gn_
•u;
flA
::1~.
1 f\"'70
~::111:..
72 Batra, Sjoberg, and Aberg
8. Spellacy, W. N.: Monitoring of high-risk pregnancies with human placental lactogen, in Spellacy, W. N., editor: Manal!:ement of the Hi!!:h-Risk Prel!:llancv, Baltimore, ~ . 1976, ~University Park Pr~ss. 9. Magiste, M .. von Schenck, H., Sjoberg, N.-0., Thorell,]., and Aberg, A.: Screening for detecting twin pregnancy, AM. j. 0BSTET. GYNECOL. 126: 697, 1976. 10. Letchworth, A. T., Boardman, R. J., Bristow, Ch., Landow, ]., and Chord, T.: A rapid semi-automated method for the measurement of human chorionic somatomammotrophin. The normal range in the third trimester and its relation to fetal weight, Br. J. Obstet. Gynaecol. 78: 542, 1971. 11. Lindberg, B. S., Lindberg, P., Martinsson, K., and Johansson, E. D. B.: Radioimmunological methods for the estimation of oestrone, oestradiol-17 .B and oestriol in pregnancy plasma, Acta Obstet. Gynecol. Scand. 32(Suppl.): 5, 1974. 12. Youssefnejadian, E., Florensa, E., Collins, W. P., and Sommerville, I. F.: Radioimmunoassay of plasma progesterone, J. Steroid. Biochem. 3: 893, 1972. 13. Batra, S., Bengtsson, L. Ph., Grundsell, H., and SjOberg.
May 1, 197tl
Am. J. Obstet. Gynecol.
14.
15. 16.
17.
18.
N .-0.: Levels of free and protein-bound progesterone in plasma during late pregnancy, J. Clin. Endocrinol. Metab. 42: 1041, 1976. Gaede, P., and Norgaard-Pedersen, B.: Serum human placental lactogen hormone concentration in the second half of pregnancy determined by a simple immunoelectrophoretic technique, Acta Endocrinol. 76: 369, 1974. Klebe, J. G., and Gaede, P.: Serum progesterone in diabetic pregnancy, Acta Endocrinoi. 75 (Suppi.): 182, 1974. Diczfalusy, E., and Mancuso, S.: Oestrogen metabolism in pregnancy, in Klopper, A., and Diczfalusy, E., editors: Foetus and Placenta, Oxford, 1969. Blackwell Scientific Publications, p. 191. Solomon, S., and Younglai, E. V.: Neutral steroids in human pregnancy. Isolation, formation, and metabolism, in Klapper, A., and Diczfalusy, E., editors: Foetus and Placenta, Oxford, 1969, Blackwell, Scientific Publications, p. 249. Duff, G. B., and Brown, J. B.: Urinary oestriol excretion in twin pregnancies, Br. J. Obstet. Gynaecol. 81: 695, 1974.
J.
131: 69, 1978.)
0BSTET. GYNECOL.
LEvELS oF human placental lactogen (HPL), as well as of ' ' ------ nl::!ct>ntal hormones such as estradiol-17 8 IE2) -- otht>r and progesterone (P), increase with advancing pregnancy.1 Due to the fact that the HPL level is significantly higher in multibirth pregnancy, 2- 8 it can be, as demonstrated recently, used as a screening test for detecting twin pregnancy. 9 Although the levels of both E2 and P, since they are also placental hormones, would be expected to be higher in multibirth pregnancy, only fragmentary data are available on this point. In fact, we are not aware of any study in which the levels of both E2 and P in twin pregnancies have been measured. Besides the fact that this kind of information in itself would be of general interest it could also prove to be of clinical aid for detecting twin pregnancy. In the present study we have compared the levels of HPL, E2, and Pin simplex pregnancies during the third trimester with those in duplex. ~-----
-----
-
-
--
-
-
-
-
-
.
From the Department of Obstetrics and Gynecology, University Hospital Lund. Supported by the Ford Foundation. Receivedfor publication April 26, 1977. Revised September 13, 1977. Accepted October I, 1977. Reprint requests: Dr. Nils-Otto Sjoberg, Department of Obstetrics and Gynecology, University Hospital, S-221 85 Lund, Sweden. 0002~9378/78/01131-0069$00.40/0
©
1978 The C. V. _r..{osby Co.
Materials and methods Blood samples were obtained seriallv from 56 women (21 to 38 years of age) between weeks 30 to 36 of pregnancy. Fifteen women were delivered of simplex and 41 of twins. HPL was estimated in the plasma by a radioimmunoassay performed according to the method described by Letchworth
Results The levels of HPL in simplex and duplex pregnancies from weeks 30 to 36 are shown in Fig. 1. In duplex pregnancies the levels of HPL were significantly higher (p < 0.005) for each week than the respective levels for simplex. Similarly, the plasma P concentration was significantly higher in duplex than in simplex pregnancies (Fig. 2). The mean levels of HPL and Pin duplex pregnancy for each week (30 to 36 weeks) were at least 60 per cent greater than in simplex. On the other hand, the levels of E2 did not show a significant difference between simplex and duplex pregnancies in any of the weeks studied (Fig. 3). Fig. 4 shows a plot of HPL and P values in all samples
69
May I, 1978
70 Batra, Sjoberg, and Aberg
Am.
J. Obstet. Gynecol.
401 Duplex 7.0
30
-"' E
Simplex
c
-
ca.
E 6.o
~
~
20
~
"C
-'
f!
Q_
;;;
I
UJ
I
10i
I
0
30
31
32
33
34
35
36
Weeks of pregnancy
Fig. 3. Mean levels (±S.E.) of estradiol-17/3 in simplex and duplex pregnancies from weeks 30 to 36.
Weeks of pregnancy
Fig. 1. Mean levels (±S.E.) of HPL in simplex and duplex pregnancies from weeks 30 to 36.
3001 250
I
Comment
200
..§
Q;
(n = 91) from twin pregnancies, irrespective of gestational length. There was a highly significant correlation (p < 0.005) between the concentrations of HPL and P in plasma from twin pregnancies. The regression line of x on y (x = 14.84 y + 105.89) is aiso shown.
150
u;
t
so
30
31
33 34 35 32 Weeks of pregnancy
36
Fig. 2. Mean level (±S.E.) of progesterone in simplex and duplex pregnancies from weeks 30 to 36.
The levels of HPL as well as other hormones of placental origin would be expected to be higher in multibirth than in unibirth pregnancy. This has been shown for HPL, and due to a significant difference between simplex and duplex pregnancies the measurement of this hormone in plasma has been used as a screening test for detecting twin pregnancy. 9 The results of the present study show that measurements of P levels could also provide a satisfactory screening test, since the levels were significantiy higher in duplex than in simplex pregnancy. Since both HPL and P are produced in the same placental cells, namely syncytiotrophoblasts, it was not surprising to find a significant correlation (Fig. 4) between the levels of these two hormones. With the exception of one study/ such a correlation between HPL and P has been reported in simplex pregnancy. 14 · 15 The present finding, showing an insignificant difference in the levels of E2 between simplex and duplex pregnancy, is somewhat puzzling in view of the fact that this hormone is also produced in the syncytiotrophoblasts. There can be several possible explanations for this unexpected finding. There is now considerable evidence that the produc-
Volume !31 Number l
Placental hormones for detecting twin pregnancy
~;;rn~
121 11
71
i
~
;;~·y
/'7
101
~
.
~
I
9 E
-;a :::1.
c
Cll
Ol
0
7
u
.!!!
iii 6
c Cll
u
a. Ill
c
Ill
E ::J
:r:
5
.I
4~
r =0.38
·j
3J
p
I I
2J
~------------T-------------~------------~------------~------------~--------·----,
100
150
300
250
200
350
400
Progesterone ng I ml Fig. 4. Relationship between the levels of HPL and progesterone in twin pregnancy plasma (n = 91). The regression lines of both yon x (y = 0.0 lx + 4.85) and x on y (n == 14.84y + 105.89) are shown
tion of P by placenta is more or less independent of the fetus. 16 · 17 The production of E2 during pregnancy is, however, to a great extent dependent on the supply of precursors from the fetus. 16 • 17 Despite th.e presence of two fetuses, there may be a limiting step either in the availability of the E2 precursors from fetus to placenta or in the synthesis of E2 in the placenta from the presursors. Another explanation might be related to a
REFERENCES
J.,
and Benirschke, K.: Principles and Management of Human Reproduction, Philadelphia, London, Toronto, 1972, W. B. Saunders Company. 2. Josimovich, J. B.: Placental lactogenic hormone, in Fuchs, F., and Klopper, A., editors: Endocrinology of Pregnancy, New York, 1971, Harper & Row, p. 184. 3. Genazzani, A. R., Cocola, F.; Neri, P., and Fioretti, P.: Human chorionic somacomammotropin (HCS) levels in norma! and pathological pregnancies and their correlation with the placental function, Acta Endocrinol. 71 (Suppl.): 167, 1972. 4. Lebech, P. E.. and Borggaard, B.: Serum levels of human I. Reid, D. E., Ryan, K.
greater dependence of E2 than P on the fetus for its metabolism. There is evidence that urinary estriol excretion in the twin pregnancies is significantly greater than in simplex pregnancies. 18 The above ex~ planations, however, must remain speculative until a more precise information on the biosynthesis and metabolism of steroids in fetus and placenta is available.
chorionic somatomammotropin (HCS) in normal and abnormal pregnancies, Acta Endocrinol. 75 (Suppl.): 182. 1974. 5. Dawood, M. Y., and Ratnam, S. S.: Serum unconjugated estradiol-17 .B in normal pregnancy measured by radioimmunoassay, Obstet. Gynecol. 44: 194, 1974. 6. Dawood, M. Y.: Circulating maternal serum progesterone in high-risk pregnancies, AM. J. OsSTET. GYNECOI .. 125: 832, 1976. 7. Conly, P. W., Spellacy, W. M., and Claveland, W. W.: Maternal plasma progesterone and human placental lactogen in the last month of full-term pregnancy, Clin. Res. Gn_
•u;
flA
::1~.
1 f\"'70
~::111:..
72 Batra, Sjoberg, and Aberg
8. Spellacy, W. N.: Monitoring of high-risk pregnancies with human placental lactogen, in Spellacy, W. N., editor: Manal!:ement of the Hi!!:h-Risk Prel!:llancv, Baltimore, ~ . 1976, ~University Park Pr~ss. 9. Magiste, M .. von Schenck, H., Sjoberg, N.-0., Thorell,]., and Aberg, A.: Screening for detecting twin pregnancy, AM. j. 0BSTET. GYNECOL. 126: 697, 1976. 10. Letchworth, A. T., Boardman, R. J., Bristow, Ch., Landow, ]., and Chord, T.: A rapid semi-automated method for the measurement of human chorionic somatomammotrophin. The normal range in the third trimester and its relation to fetal weight, Br. J. Obstet. Gynaecol. 78: 542, 1971. 11. Lindberg, B. S., Lindberg, P., Martinsson, K., and Johansson, E. D. B.: Radioimmunological methods for the estimation of oestrone, oestradiol-17 .B and oestriol in pregnancy plasma, Acta Obstet. Gynecol. Scand. 32(Suppl.): 5, 1974. 12. Youssefnejadian, E., Florensa, E., Collins, W. P., and Sommerville, I. F.: Radioimmunoassay of plasma progesterone, J. Steroid. Biochem. 3: 893, 1972. 13. Batra, S., Bengtsson, L. Ph., Grundsell, H., and SjOberg.
May 1, 197tl
Am. J. Obstet. Gynecol.
14.
15. 16.
17.
18.
N .-0.: Levels of free and protein-bound progesterone in plasma during late pregnancy, J. Clin. Endocrinol. Metab. 42: 1041, 1976. Gaede, P., and Norgaard-Pedersen, B.: Serum human placental lactogen hormone concentration in the second half of pregnancy determined by a simple immunoelectrophoretic technique, Acta Endocrinol. 76: 369, 1974. Klebe, J. G., and Gaede, P.: Serum progesterone in diabetic pregnancy, Acta Endocrinoi. 75 (Suppi.): 182, 1974. Diczfalusy, E., and Mancuso, S.: Oestrogen metabolism in pregnancy, in Klopper, A., and Diczfalusy, E., editors: Foetus and Placenta, Oxford, 1969. Blackwell Scientific Publications, p. 191. Solomon, S., and Younglai, E. V.: Neutral steroids in human pregnancy. Isolation, formation, and metabolism, in Klapper, A., and Diczfalusy, E., editors: Foetus and Placenta, Oxford, 1969, Blackwell, Scientific Publications, p. 249. Duff, G. B., and Brown, J. B.: Urinary oestriol excretion in twin pregnancies, Br. J. Obstet. Gynaecol. 81: 695, 1974.