British Journal of Obstetrics and Gynaecology May 1978. Vol85. pp 348-350

CIRCULATING LEVELS OF ALPHA-FETOPROTEIN AND PREGNANCY SPECIFIC GLYCOPROTEIN IN PREGNANCIES WITHOUT A N EMBRYO BY

M. J. BENNETT* John Radclifle Hospital, Oxford

J. G. GRUDZINSKAS Y. B. GORDON St Bartholomew’s Hospital, London AND

A. C . TURNBULL John Radclifle Hospital, Oxford Summary Ten patients with depressed serum alpha-fetoprotein (AFP) levels at 14 to 15 weeks gestation were found to have no embryo on ultrasonography: two patients had hydatidiform moles and the remainder had anembryonic pregnancies (blighted ova). The pregnancy specific p1 glycoprotein (SP,) levels in serum were measured in all these ten patients. Seven of the eight patients with anembryonic pregnancies and one of the two patients with molar pregnancies had low serum SP, levels. These observations suggest that the measurement of AFP and SP, may provide biochemical evidence of pregnancy without an embryo.

ANEMBRYONIC pregnancy due to a blighted ovum is a major cause of spontaneous abortion in the first trimester of pregnancy (Fujikara et al, 1966; Robinson, 1975). Because the clinical diagnosis of a blighted ovum is extremely difficult, particularly in patients presenting with threatened abortion, a number of other parameters have been used including ultrasound (Robinson, 1975) and the measurement of steroids and proteins produced by the fetoplacental unit (Niven et al, 1972; Garoff and Seppala, 1974; Duff, 1975). Our study was initiated to assess the clinical significance of depressed serum levels of alphafetoprotein (AFP) during midtrimester screening

for a neural tube defect. A comparison was then made with the ultrasound findings and the circulating levels of pregnancy specific p1 glycoprotein (SP,). SP, is one of a new generation of recently identified pregnancy specific proteins which is produced by the trophoblast during pregnancy (Bohn, 1971). METHODS Patients with depressed serum levels of AFP, measured as part of a prospective survey in the Oxford area, were referred to one of us (M.J.B.) for further assessment at 14 or 15 weeks gestation. An ultrasound examination was performed using a Nuclear Enterprises Diasonograph NE 4102, to determine the presence of a fetus, fetal viability and to estimate the gestational sac volume. Ultrasound diagnosis

* Present address: Queen Charlotte’s Maternity Hospital, London. 348

AFP AND SP1 IN PREGNANCIES WITHOUT EMBRYOS

of an anembryonic pregnancy was made if there was a gestation sac with a volume of greater than 2.5 ml and no fetal echoes were present. A serum sample was collected and stored at -20°C until assayed for SP, (Grudzinskas et al, 1977) and AFP (Hoechst Reagent kit). In the presence of a blighted ovum on ultrasound, an evacuation of the uterus was performed and the products of conception subjected to a histological examination to exclude fetal parts. RESULTS Of about 60 patients who had an ultrasound scan because of low serum AFP levels, ten had no embryo; two patients had a hydatidiform mole and the remainder had anembryonic pregnancies. The circulating AFP levels were below the 10th centile (10 pg/l at 15 weeks) in all patients (Table I). The SPI levels were TABLE I Circulating levels of AFP and SP, in pregnancies without an embryo

Patient

Gestational AFP age (weeks)

SP1 (mg/l)

1 2 3 4 5 6 7 8 9

15 15+ 15+ 14+ 14 I5+ 15 14 15f

1.0 9.0 8.0 3.0 9.0 1.0 7.0 6.0 8.0

0.4 0.4 6.2 5.4 6.4 4.6 5.0 17.0 27.0

10

14

1.0

5.0

Diagnosis Blighted ovum

Hydatidiform mole

349

has received little attention, mainly because anencephaly and spina bifida are associated with markedly elevated levels. This study has shown that in some patients low serum AFP levels indicate the presence of an anembryonic pregnancy. This finding is not surprising, as the major site of production of AFP is the fetal liver (Gitlin et at, 1972). However, AFP may be produced even in the absence of a fetus (Leek et al, 1974). The clinical significance of circulating levels of SP, has recently been evaluated in both late pregnancy (Gordon et al, 1977; Tatra et al, 1974; Horne et al, 1977), and early pregnancy (Grudzinskas et al, 1977). In our study, circulating SP, levels were depressed in all but two subjects, indicating that this parameter may be useful in determining the outcome of pregnancy in threatened abortion. The mechanisms controlling the production of proteins by the trophoblast are unknown, however, the reduced levels of SP1 in a blighted ovum would imply that a fetus is necessary to ensure optimal production. In our study, AFP levels were the initial indication for ultrasound scanning. Although ultrasound is the most accurate method of diagnosing an anembryonic pregnancy, biochemical testing seems to provide a means of screening for abnormalities other than neural tube defects (Brock et al, 1977; Wald et al, 1977).

ACKNOWLEDGEMENT J.G.G. is supported by the World Health Organization. REFERENCES

below the 10th centile (10 mg/l at 15 weeks) in all but two patients (Table I, No. 8 and 9), one of whom had a molar pregnancy. No evidence of fetal parts was found in any of the patients studied.

DISCUSSION Routine screening for neural tube defects using circulating levels of AFP in the second trimester of pregnancy is now commonplace in many parts of Britain. To date, however, the diagnostic significance of depressed levels

Aschheim, S., and Zondek, B. (1972): Klinische Wochenschrif, 6,13. Bohn, H. (1971): Archiv fur Gynakologie, 210,440. Brock, D. J. T., Barron, L., Jelen, P., Watt, M., and Scrimgeour, J. B. (1977): Lancet, 2,267. Duff, G. B. (1975): British Journal of Obstetrics and Gynaecology, 82, 858. Fujikara, T., Froehlich, L. A., and Driscoll, S. G. (1966): American Journal of Obstetrics and Gynecology, 95,902. Garoff, L., and Seppala, M. (1974): American Journal of Obstetrics and Gynecology, 121,257. Gitlin, D., Perricelli, A., and Gitlin, G. M. (1972): Cancer Research, 32, 979.

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BENNETT, GRUDZINSKAS, GORDON AND TURNBULL

Gordon, Y.B., Grudzinskas, J. G., Jeffrey, D., Chard, T., and Letchworth, A. T. (1977): Lancet, 1, 331. Grudzinskas, J. G . ~Gordon, y. Jeffrey, D-, and Chard, T. (1977): Lancet, 1, 333. Home, C. H. W., Jandial, V., and Towler, C. M. (1977): International symposium of Hypertensive Disorders (in Dress). Leek; A: E., Kitau, M. J., and Chard, T. (1974): Lancet, 2, 1088. B.y

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Circulating levels of alpha-fetoprotein and pregnancy specific beta1 glycoprotein in pregnancies without an embryo.

British Journal of Obstetrics and Gynaecology May 1978. Vol85. pp 348-350 CIRCULATING LEVELS OF ALPHA-FETOPROTEIN AND PREGNANCY SPECIFIC GLYCOPROTEIN...
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