J. G. Grudzinskas

FETAL LOSS AFTER IMPLANTATION: A Prospective Study

The incidence of post-implantation pregnancy loss in 197 women was determined prospectively. The diagnosis of pregnancy was based on the detection of human chorionic gonadotropin in the urine during the luteal phase of each menstrual cycle. There were 152 conceptions in the 623 cycles studied with a pregnancy loss rate of 43%. 14 of the pregnancies ended in clinically recognised spontaneous abortions and in 50 the sole evidence of pregnancy was an increased concentration of urinary hCG. The maximum conception rate achieved was 36% in the first cycle after removal of an intra uterine device.

SPECIFIC AND SENSITIVE DETERMINATION OF PREGNANCY-SPECIFIC β1-GLYCOPROTEIN BY RADIOIMMUNOASSAY: A New Pregnancy Test

A specific and highly sensitive radioimmunoassay (R.I.A.) for determination of pregnancy-specific beta 1-glycoprotein (S.P.1) in human plasma, urine, amniotic fluid, and breast milk has been developed. The minimum detection limit of S.P.1 was 8 mug/1 of sample. The assay was applied to plasma and/or urine samples from 8 women in early pregnancy. S.P. 1 was detected in the plasma of all three women obtained within 14 days of ovulation, the earliest positive result being at 7 days. In another woman plasma was negative at day 18 and positive by day 22. In the three remaining women plasma S.P.1 was detected when measured within 24 to 36 days of ovulation. S.P.1 was detected in four urine samples obtained between 20 and 28 days after ovulation. S.P.1 was also measured in breast milk, amniotic fluid, cord blood, and plasma of women with ectopic gestation and trophoblastic disease. It is suggested that the assay of S.P.1 may have important advantages over existing systems for detection and monitoring of early pregnancy.

CONCENTRATIONS OF PREGNANCY-SPECIFIC β1-GLYCOPROTEIN IN MATERNAL BLOOD IN NORMAL PREGNANCY AND IN INTRAUTERINE GROWTH RETARDATION

A radioimmunoassay has been developed for pregnancy-specific beta 1-glycoprotein (S.P.1), a product of the human placenta. Circulating concentrations of S.P.1 were measured in 153 women in the third trimester of normal pregnancy and in 27 women who delivered children with birth-weight below the 10th centile of the normal range--i.e., with intrauterine growth regardation (I.U.G.R.). Concentrations of S.P.1 showed a skewed distribution and rose progressively to reach a plateau in the last four weeks of pregnancy. In over 70% of women with I.U.G.R. of the fetus, concentrations of S.P.1 were low. Measurement of serum-S.P.1 may provide a new index of fetal wellbeing.

CIRCULATING LEVELS OF PREGNANCY‐SPECIFIC β1‐GLYCOPROTEIN IN EARLY PREGNANCY

Circulating levels of pregnancy‐specific β1‐glycoprotein (SP1 or PSβG), luteinizing hormone (LH) and human chorionic gonadotrophin (HCG) were measured serially in 9 subjects immediately after conception. Ovulation occurred spontaneously in 3 subjects, or followed administration of clomiphene citrate (2 subjects) or bromocriptine (4 subjects). The timing of ovulation was determined by the appearance of the LH surge. Levels of HCG were detected 10 to 16 days, and SP1, 18 to 23 days after ovulation. These findings suggest that the measurement of plasma levels of SP1 may provide valuable additional biochemical evidence of pregnancy.

Placental protein 5 in fetal and maternal compartments.

Placental protein 5 is produced by the syncytiotrophoblast and secreted into the maternal peripheral circulation reaching levels of approximately 30 μg per litre in normal pregnancy at term. In the present study the distribution of PP5 was examined in maternal and fetal compartments in 13 patients at delivery.

CIRCULATING LEVELS OF PREGNANCY PROTEINS IN EARLY AND LATE PREGNANCY IN RELATION TO PLACENTAL TISSUE CONCENTRATION

The concentrations of human chorionic gonadotrophin (hCG), human placental lactogen (hPL), pregnancy specific β1 glycoprotein (SP1), ferritin (PP2) and placental protein 5 (PP5) were examined in maternal serum and placental tissue in early and late pregnancy. The circulating concentration of hPL, SP1, and PP5 were higher during late pregnancy than early pregnancy, that of hCG lower, and ferritin (PP2) levels showed no difference. Placental tissue levels of hPL and SP1 were higher in late pregnancy, hCG levels lower, and ferritin (PP2) and PP5 showed no change. The ratio of the concentration in maternal serum to that in placental tissue increased during pregnancy for all proteins with the exception of ferritin. It is proposed that the mechanism of secretion of trophoblast specific proteins varies widely and that this should be taken into account in the clinical interpretation of circulating levels in the mother.

CIRCULATING LEVELS OF PREGNANCY SPECIFIC β1 GLYCOPROTEIN IN PREGNANCIES COMPLICATED BY DIABETES MELLITUS

Circulating levels of SP1 were measured in 20 insulin dependent diabetic women during the third trimester of pregnancy. With one exception, SP1 levels were between the 80 percent confidence limits of the normal range. The exception was a patient who was delivered of a normal infant at 37 weeks but had consistently low levels of SP1 from 32 weeks until delivery, suggesting a specific defect in SP1 synthesis.

CIRCULATING LEVELS OF ALPHA‐FETOPROTEIN AND PREGNANCY SPECIFIC β1 GLYCOPROTEIN IN PREGNANCIES WITHOUT AN EMBRYO

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 β1 glycoprotein (SP1) 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 SP1, levels. These observations suggest that the measurement of AFP and SP1 may provide biochemical evidence of pregnancy without an embryo.

DISAPPEARANCE OF PREGNANCY-SPECIFIC β1 GLYCOPROTEIN FROM THE MATERNAL CIRCULATION AFTER DELIVERY

It is likely that there are systematic differences between circulating pregnancy‐specific β1 glycoprotein (SP1) levels measured by radioimmunoassay and immunoprecipitation systems. We have re‐investigated the decline in circulating levels of SP1 following delivery of the placenta. Serial blood samples were collected for 120 hours from 10 women following Caesarean section or vaginal delivery at term. The apparent half‐life of SP1 after delivery ranged between 17 and 45 hours.