Alexander C. Turnbull

THE HUMAN PLACENTA AND MEMBRANES: A HISTOLOGICAL AND IMMUNOFLUORESCENT STUDY OF THE EFFECTS OF INTRA‐AMNIOTIC INJECTION OF HYPERTONIC SALINE

INJECTION of hypertonic solutions into the amniotic sac effectively induces abortion in the second trimester of pregnancy or labour in the third trimester. Since the foetus usually dies, the technique should only be used to terminate pregnancy when the foetus is previable, grossly abnormal or dead. The mechanism by which this procedure causes the uterus to expel its contents has not yet been elucidated. There is even disagreement on the nature of the changes produced in the placenta and membranes after intra-amniotic injection of hypertonic solutions. The lesions described have included necrosis of amnion (Stamm and de Watteville, 1954), an intense “necrotising placentitis” (Bengtsson and Stormby, 1962), intervillous thrombosis (Jaffin et al., 1962) and thrombosis of chorionic vessels with chorioamnionitis (Sciarra et al., 1964); other workers did not detect any changes in the placenta and membranes (Timonen et a/., 1962; Wood et a/., 1962). This paper describes the histological appearances of the placenta and membranes with the standard methods of fixation and staining in cases in which hypertonic saline had been injected into the amniotic sac during either the second or the third trimester of pregnancy and contrasts these appearances with those from cases with spontaneous onset of labour. In addition, recently developed immunofluorescent techniques have been used to trace in the damaged and apparently undamaged areas of the placenta the histological localization of certain serum proteins, a placental antigen which crossreacts with an antiserum to human pituitary growth hormone, a cytoplasmic antigen present in all cells known or believed to produce steroid hormones, and certain antigens in cell nuclei which react with antinuclear antibodies in the sera of patients with systemic lupus erythematosus. These methods were used in the hope that we might obtain an indication of the viability and endocrine function of the damaged and apparently normal areas of the placenta.

Changes in uterine contractility following intra-amniotic injection of hypertonic saline to induce therapeutic abortion.

DESPITE much research the mechanism which controls the onset of labour remains unsolved. As assessed by uterine contractility, labour may be preceded by a period of increased activity sometimes lasting several weeks or may commence without warning so that the recording of the sequential changes is time consuming and difficult. By comparison, strong uterine contractions begin quickly after hypertonic saline has been injected into the amniotic sac of the quiescent uterus at mid-pregnancy to induce therapeutic abortion (Aburel, 1938) and the sequence of events can be studied according to a pre-arranged plan. It may be argued, of course, that the uterine contractions induced by hypertonic saline in early pregnancy have little in common with the uterine contractions of normal labour at term, but Bengtsson and Csapo (1962) state that in both cases the uterus contracts vigorously because it has been freed from the restraining influence of the progesterone produced by the placenta, which they claim “blocks” the conduction of excitation waves through the myometrium over the placenta. Bengtsson and Stormby (1962) believe that the hypertonic saline exerts its effect by causing a “necrotizing placentitis” and report a fall in the urinary excretion of pregnanediol in these cases, although Short et al. (1965) found no change in the concentration of progesterone in uterine venous blood after intra-amniotic injection of saline. Wood, Booth and Pinkerton (1962) showed that intra-amniotic injection of hypertonic glucose effectively induced labour in patients with an anencephalic foetus or a dead foetus. It is impossible to study the endocrine mechanisms of normal labour in these patients since steroid hormone production is known to be abnormal in such cases. We have had the opportunity to investigate the effect of hypertonic saline used to induce abortion in normal pregnancies which had reached at least 19 weeks. Continuous records of uterine activity have been made before and after the saline injection, up to the time of abortion. Most previous studies report only intermittent measurements of contractility. Wiqvist and Eriksson (1964) attempted a quantitative analysis but onIy recorded activity for the first eight hours after the saline injection or in the 20th hour after saline or in the hour before abortion. In our view, only continuous recordings, analysed in detail, can give an adequate picture of the sequence of events and the variation in the strength and frequency of uterine contractions.

The relationship between amniotic fluid pressure and uterine wall tension in pregnancy.

Abstract The theoretical relationship between amniotic fluid pressure and myometrial tension in the pregnant human uterus has been studied using physical laws relating to fluid-filled cavities, and measurements of frozen sections of the pregnant human uterus published by Ivy. 7 The size of the uterine cavity is one of the main factors influencing the amniotic fluid pressure/myometrial tension relationship. The same tension will raise the amniotic fluid pressure much more in a smaller uterus than in a large one. In uteri of the same size, however, tension is directly proportional to amniotic fluid pressure. These data can be used to show that the very high intrauterine pressure recorded during contractions in early or midpregnancy abortions or in the puerperium are, in terms of myometrial tension, no greater than would be found in normal labor at term.

EFFECTS OF PRE‐ECLAMPSIA ON THE CHANGES IN IODINE METABOLISM DURING PREGNANCY

STUDIES of iodine metabolism in man are frequently based on observing the manner in which the thyroid gland and the kidney remove iodine from the plasma. The measures obtained in the investigation of these functions are the thyroid clearance and the renal clearance of radioactive iodine respectively. While these values provide indices of the metabolism of stable iodine (as opposed to radioiodine) it is necessary to ascertain the plasma level of stable iodine at the same time to obtain the absolute amounts of iodine removed from the blood by the thyroid and the kidney. The former is an extremely important measure, described as the absolute iodine uptake, since it is a more direct indicator of thyroid hormone production than the thyroid clearance of radioiodine alone. The changes in iodine metabolism during normal pregnancy have been measured by Aboul-Khair et al. (1964) using the short-lived isotope 7321. Renal clearance of iodine increased early in pregnancy and remained high throughout. The plasma inorganic iodine fell but a compensatory increase in thyroid clearance of iodine maintained the absolute iodine uptake by the thyroid within normal limits. All these changes gradually regressed to normal after delivery, but non-pregnant levels were not reached until between the sixth and twelfth week after delivery.