J. de Haan

Gossypol – a New Antifertility Agent for Males

Gossypol is capable of inhibiting the fertility of male rats. On administration of gossypol the spermatids are damaged first. With the increase in dosage and duration of treatment the spermatocytes are also damaged. In the epidymis there are exfoliated spermatids and spermatocytes with numerous dead spermatozoa many of which had their heads and fails separated. The sperm count gradually decreases until azoospermia. Electron microscopic examinations reveal changes in the acrosomes and mitochondrial spiral sheath. Interstitial cells of the testis seemed to be unaffected. Over 4,000 healthy men have been on gossypol for more than 6 months. The antifertility efficacy evaluated by semen examination is 99.89%. Side effects are mild and of low incidence. A few of the subjects are found to be hypokalemic. However, it remains to be elucidated if gossypol is related to the development of hypokalemia.

Mechanisms of late decelerations in the fetal heart rate. A study with autonomic blocking agents in fetal lambs.

Fetal heart rate decelerations resembling the late deceleration FHR pattern were produced in fetal sheep by periodic occlusion of the maternal common hypogastric artery for 30-60 sec. Transient fetal hypertension also occurred during the occlusions. Alpha-adrenergic blockade with phentolamine eliminated or markedly reduced the hypertensive response. FHR decelerations still occurred intermittently with some occlusions; however, their character was greatly altered. After parasympathetic blockade with atropine, the decelerations were replaced by periodic FHR accelerations during the occlusions. These accelerations were, in turn, eliminated by the beta-adrenergic blocking agent, propranolol. In the presence of combined parasympathetic, alpha- and beta-adrenergic blockade, the FHR remained essentially constant during the hypogastric artery occlusions in non-acidemic fetuses. FHR decelerations persisted after parasympathetic or total autonomic blockade when the fetuses were significantly hypoxic, as judged by depressed arterial blood pH and base excess values. Beat-to-beat variability of the baseline FHR persisted in the face of severe hypoxia and acidosis. These observations demonstrate that reflex mechanisms are involved importantly in the genesis of late deceleration FHR patterns in the acutely hypoxemic fetus, but that direct depression of myocardial rhythmicity becomes a factor as hypoxic acidosis develops.

The effect of diazepam administration during pregnancy or labor on the heart rate variability of the newborn infant

Maternal diazepam medication during labor reduces beat-to-beat variability of the fetal heart rate. In this study, the prolongation of the effect was examined in the newborn. The mother received diazepam: (A) during labor as a tranquilizer, (B) daily in low doses at the end of pregnancy, or (C) in high doses i.v. for (pre-)eclampsia. A control group had no analgesic or sedative during pregnancy or labor. The electrocardiogram (ECG) was recorded daily from each newborn during the first 6 days after birth. After preprocessing of the ECG, the median R-R interval, the long-term irregularity index (LTI index) and the interval difference index (ID index) were calculated. A cubic spline interpolation method was applied to compare the various groups with respect to these heart rate parameters. The median R-R interval showed no particular differences in trend for all groups. The LTI index was decreased in the first days after birth in the chronic diazepam (B), and in the diazepam infusion groups (C), but statistical significance was not reached. The ID index was significantly decreased in the first 1-2 days in the newborns of the acute and chronic diazepam group. In the diazepam infusion group, an even longer lasting effect was observed. Maternal diazepam medication affects the beat-to-beat variability in the newborn. The duration of the effect is dependent on dosage and route of administration.

Predictive Value of Uterine Contractility and the Serum Levels of Progesterone and Oestrogens with Regard to Preterm Labour

A longitudinal investigation regarding the serum concentrations of oestradiol, oestriol and progesterone in relation to uterine activity has been performed in 80 healthy primigravid women during the course of pregnancy up to the 37th week of pregnancy. The frequency of uterine contractions was quantitatively objectivated by means of external toco-dynamometry; simultaneously the uterine activity has been recorded by the pregnant women qualitatively. It appears that there is a gradual increase of all the three mentioned hormones during the course of pregnancy. However, there is a large interindividual spread. There exists no relation between the hormonal serum levels and uterine activity (quantitatively as well as qualitatively recorded). Between these two latter there is a poor relation. It is impossible to predict the occurrence of preterm birth based on hormonal serum changes. This holds for the progesterone-oestradiol ratio.

The preejection period of the fetal cardiac cycle. I. Umbilical cord occlusions.

The preejection period (PEP) of the fetal cardiac cycle was studied in the chronically instrumented fetal lamb. A specially constructed device permitted the occlusion of either both umbilical veins, or of both umbilical arteries, or of the total umbilical cord. A prolongation of the PEP together with an increase in blood pressure was a consistent finding during any type of cord occlusion. In poorly oxygenated fetal lambs a two-step increase in the duration of the PEP was observed during the occlusion. It was accompanied by a simultaneous two-step increase in fetal arterial blood pressure. A correlation was found between the steady-state fetal pO2 before the occlusion and the increase in fetal arterial diastolic blood pressure during the blockade of the umbilical circulation. During occlusion the main determining factors of the PEP prolongation appear to be the increase in afterload and the decrease in preload of the fetal heart. The second step in the prolongation of the PEP during the occlusions in poorly oxygenated fetal lambs is attributed to a chemoreceptor-induced reflex, resulting in a redistribution of cardiac output in the fetal lamb.

Computed tomography in staging untreated patients with cervical cancer

In a study to test the accuracy of computed tomography (CT) in staging untreated patients with cervical cancer, the interpretations of the CT scans of pelvis and abdomen of 56 consecutive patients were compared with surgical and/or clinical findings. This study clearly demonstrates that CT is unreliable in diagnosing parametrial tumour invasion and that it is not justified to make the therapeutically important differentiation between a IB or IIB stage with CT. In demonstrating metastatic lymph nodes, the accuracy of CT was only 75%, predominantly due to metastatic deposits in normal-sized nodes. CT was less accurate in diagnosing bladder wall and sigmoid invasion than cystoscopy and sigmoidoscopy, respectively, and was as accurate as urography in diagnosing ureteric obstruction. For these reasons, CT is not indicated as a routine procedure in cervical cancer staging, particularly not in the early stages of the disease. CT may be helpful in the higher clinical stages to measure tumour bulk and to get an impression about the whole extent of the disease.

The preejection period of the fetal cardiac cycle. II. Maternal common internal iliac artery occlusions

The preejection period (PEP) of the fetal cardiac cycle was studied in the chronically instrumented fetal lamb. An inflatable cuff occluder was positioned around the maternal common internal iliac artery, the pregnant ewes main uterine blood-supplying vessel. Occlusion of the maternal common internal iliac artery produced a fall in pO2 and pH and a rise in pCO2. Fetal arterial blood pressure increased and PEP shortened, especially in the longer lasting occlusions. Fetal heart rate exhibited a bradycardia also during this type of occlusion. The fetal lambs cardiovascular adjustments to biochemical changes caused by occlusion of the maternal uterine blood supply appear to be determined during the initial phase of occlusion by a chemoreceptor reflex-induced peripheral vasoconstriction mediated by the adrenergic nervous system. The condition is comparable to the one observed during the second part of the umbilical cord occlusions. The interaction between a supersensitive fetal myocardium and the adrenal release of catecholamines may play a dominant role during the second part of occlusion in the longer lasting experiments. Increase in peripheral resistance in the course of redistribution of blood flow during hypoxemia induces a prolongation of the PEP in the early phase of occlusion; overriding of this effect by an increase in myocardial contractility due to rising levels of adrenal catecholamines abbreviates the PEP in the later part of the longer lasting occlusions.

Endometrial Ossification: Unilateral Manifestation in a Septate Uterus

The occurrence of bone in endometrial stroma of a 31-year-old nulligravida who attended the outpatient clinic for infertility (Ziekenhuis Annadal, Department of Obstetrics and Gynaecology, State University Limburg, The Netherlands) is described. A review of the literature is given and the theories about the etiology are discussed. It seems apparent that in the described patient, only a locally acting cause can explain the findings.

Ultrasound Increases the Prognostic Value of the Postcoital Test

The prognostic value of the postcoital (PC) test was studied in two groups of women in whom the infertility workup differed only in the way the PC test was timed. Fifty patients were investigated in a traditional way. In this group the PC test failed to have any substantial prognostic value. In a second group consisting of 54 patients, the PC test was timed applying ultrasonographic criteria for ovarian follicular development. This resulted in a highly significant prognostic test. Timing of the PC test by ultrasound enhanced both the reliability and the efficacy of the standard fertility investigation.

The lecithin/sphingomyelin ratio in Macaca arctoides.

The amniotic fluid lecithin/sphingomyelin ratio (L/S ratio) of stumptail macaque monkeys (Macaca arctoides) was investigated by means of serial amniocenteses during the second half of pregnancy. Ten dated pregnancies were studied in 9 individual monkeys. The mean number of successful amniocenteses per pregnancy was 4. A rapid increase in the L/S ratio suggesting maturation of lung surfactant synthesis occurred as early as 130--140 days of pregnancy in some animals, and as late as 150--160 days in others. The earliest and latest times at which the L/S ratio first exceeded 2.0 were 135 and 164 days, respectively. These observations indicate that the L/S ratio of M. arctoides follows a course similar to that observed in human pregnancy, with a rise at 0.7--0.8 of term gestation. M. arctoides thus appears to be a useful model for the study of factors affecting fetal lung maturity, on the basis of the amniotic fluid L/S ratio. In particular, a rapid rise in L/S ratio before 130 days of pregnancy would be highly suggestive of accelerated maturation of pulmonary surfactant production.