The effects of an increase in endogenous oestrogen on the haemostatic mechanism.

The effects on the haemostatic mechanism of rises in circulating human oestrogen in a group of women being treated for infertility with pituitary hormones were studied. Despite large but brief rises in oestrogen levels no changes were found.

Non-protein-bound oestradiol and progesterone in human peripheral plasma before labour and delivery.

Plasma samples were obtained at weekly intervals from the peripheral circulation of 12 women in the last 2-7 weeks of pregnancy. The concentrations of oestradiol and progesterone (isolated by chromatography) were measured by radioimmunoassay; the proportion of each hormone which was not bound to protein was measured by steady-state gel filtration. From these, the apparent concentration of the non-protein-bound form of each hormone was calculated. The mean proportion of oestradiol not bound to protein varied from 0.84 to 2.71% in the different subjects, but within each subject variation was within experimental error. For progesterone, the mean proportion not bound to protein in the different subjects varied from 1.76 to 2.77%; within individuals the proportion remained essentially constant. There was no consistent, recognizable trend as labour approached in the concentration of oestradiol; the concentration of progesterone; the concentrations of non-protein-bound oestradiol or non-protein-bound progesterone; the ratio of the concentrations of progesterone and oestradiol; the ratio of the concentrations of non-protein-bound progesterone and oestradiol. In nine out of 12 subjects, the ratio of the concentration of non-protein-bound progesterone to that of non-protein-bound oestradiol was greater than the corresponding ratio based on total hormone concentrations. These results therefore provide no support for the hypothesis that human labour is preceded by alteration in the progesterone to oestradiol ratio which can be detected by measurement of these hormones in peripheral blood.

Autoantibodies to soluble cellular antigens in unexplained recurrent abortion and infertility.

In 36 women with unexplained primary recurrent abortion, 13 with secondary unexpained recurrent abortion, 25 with primary unexplained infertility, 7 with secondary unexplained infertility and two groups of control women, autoantibodies to soluble cellular antigens were measured by Western blotting to a disaggregated HeLa cell antigen preparation, by counter immunoelectrophoresis and by indirect immunofluorescence. Using Western blotting the women with primary infertility and those with secondary recurrent abortion had a significantly higher prevalence of autoantibodies (P less than 0.01 in each case). This was not shown using the other methods. It is possible that these antibodies could be causally related to the pathology of the conditions studied.

Ovulation induction in clomiphene nonresponsive patients: the place of pulsatile gonadotropin-releasing hormone in clinical practice.

Seventy-three treatment courses of pulsatile gonadotropin-releasing hormone (GnRH) were given to 19 patients with clomiphene nonresponsive anovulatory infertility. Fifty cycles were given by the subcutaneous route, and 23 were given intravenously. Doses varied between 1 and 40 micrograms per pulse given at 60- or 90-minute intervals. Luteal support was either by continuation of the pulsatile GnRH or by human chorionic gonadotropin injections. In 16 cycles, potentially fertile ovulation occurred, and three pregnancies resulted, of which one continues normally. Only one of the three pregnancies occurred during intravenous GnRH treatment, and it is likely that this patient would have responded to subcutaneous treatment. The optimum dosage to induce ovulation ranged between 10 and 20 micrograms per pulse at a frequency of 60 to 90 minutes. Those patients who responded to treatment were all of normal or low body weight for their age and frame. Conversely, those who failed to respond to pulsatile GnRH with ovulation were obese except for one patient with the polycystic ovary syndrome. Because pulsatile GnRH treatment is simple and potentially safe to administer, a therapeutic trial is indicated in patients of low to normal body weight who fail to respond to clomiphene. Where patients are responsive to pulsatile GnRH, the ovulations produced are likely to be fertile, possibly because of the endogenous nature of the ovulatory luteinizing hormone surge.

Depletion of circulating T lymphocytes in pregnancy.

Changes were assessed in lymphocyte sub-populations in various stages of human pregnancy. The percentage and absolute number of E-RFC decreased during pregnancy. There was a concomitant rise in the percentages of EAC-RFC and cells bearing SmIg with little change in their absolute numbers. EAC-RFC continued to rise post-natally.

Early discharge following vaginal hysterectomy.

OBJECTIVE: To assess the feasibility of discharging selected patients home within 72 h of vaginal hysterectomy. DESIGN: Women for whom vaginal hysterectomy was planned and who were invited to take part. Those who accepted were visited at home by a staff nurse experienced in gynaecology to assess home conditions and family support. If these were suitable, the general practitioner was informed and invited to comment. If the operation was uneventful women were discharged on the third post operative day and visited at home by the nurse until the seventh day. SETTING: Leeds Western Health Authority. MAIN OUTCOME MEASURES: The number of minor complications requiring treatment by the general practitioner, the readmission rate and the acceptability to the woman and her family. RESULTS: For 11 out of 61, home conditions proved unsuitable for early discharge. In six of the remaining 50, abdominal hysterectomy proved preferable to vaginal. Thirty women were discharged home on the third day after vaginal hysterectomy, five on the fourth and seven on the fifth. Two developed urinary tract infections, treated by their general practitioners. Two required readmission to hospital. Twenty-eight of 30 discharged on the third post operative day and nine of 12 discharged on the fourth or fifth post operative day were enthusiastic about the scheme. CONCLUSIONS: Early discharge following uncomplicated vaginal hysterectomy in selected patients appears to be a safe procedure, appreciated by the majority of women. Its adoption as a routine procedure would enable the surgical throughput in a unit to be maintained on a smaller bed complement.

Antigenicity of trophoblast and possible antigen-masking effects during pregnancy.

The interaction between cultured human trophoblast cells and materanl lymphocytes was used as an in vitro model to investigate trophoblast antigenicity. Cytotoxic effects in the trophoblast monolayer were apparent after 72 hr incubation and depended on the presence of non-lymphoid cell types in addition to lymphocytes. Lysis of trophoblast was preceded by blast cell formation and apparently involved close contact between the maternal cells and the trophoblast cells. The nature of the cytotoxic reaction suggested the presence of histocompatibility factors on trypsinized trophoblast cells. This manifestation could be due to removal of fibrinoid or enhancing antibody from the cultured cells. The ability of trypsinized trophoblast cells to synthesize mucoprotein was investigated by the Hale colloidal iron test and found to be unimpaired. The effect of maternal serum on the recognition of human trophoblast antigens by maternal lymphocytes was used as an in vitro model to investigate the occurrence of enhancing antibody in maternal serum. The cytotoxic effects of maternal lymphocytes on trophoblast were completely prevented by the presence of maternal serum, this protective effect being reduced significantly by removal of IgG from the maternal serum. A slight protective effect of allogeneic pregnancy serum was also observed. It is suggested that these findings support a role for immunological enhancement in maintaining the foetal allograft.

Outcome in patients with post-pill amenorrhoea.

Ninety-six patients who developed amenorrhoea following the use of oral contraceptives were studied in two groups; one with a history of regular periods and the other with irregular periods prior to the use of oral contraceptives. Pregnancy rates were similar in patients with and without a previous history of menstrual dysfunction. Thirty-nine of 47 patients who desired pregnancy and in whom there was no definable factor inhibiting pregnancy, succeeded in conceiving.

PIP: This study reports on the resumption of menstruation and of pregnancy in women with postpill amenorrhea. 96 patients, aged 18-36, who had been on different types of oral contraception (OC) for periods varying from 3 to 108 months, were investigated. Before OC treatment 45 had regular cycles (group 1), and 51 had suffered from menstrual irregularities (group 2). Ovulation induction therapy was employed when necessary. 26 patients in group 1 resumed spontaneous ovulation and 6 achieved pregnancy; 19 patients in group 2 resumed spontaneous ovulation and 7 conceived. 18 patients in group 1, and 18 patients in group 2 underwent ovulation induction therapy mostly with gonadotropins; 12 achieved pregnancy in group 1 and 14 in group 2. Of the 96 patients 31 did not wish to conceive, 7 were lost to follow-up, 7 had primary gonadal failure, 2 had undergone tubal occlusion, and the husbands of the remaining 2 had oligospermia. Of the remaining 47 patients 39 conceived, or a pregnancy rate of 82%; more specifically, a pregnancy rate of 81% in group 1, and of 84% in group 2. These results show that treatment for patients with previous irregular cycles resulted in pregnancy rates comparable to those of patients without menstruation disorders prior to OC treatment.

Blood pressure, plasma osmolarity and oedema in pregnancy.

Relations of mean arterial pressure to age, parity, plasma, osmolarity, sodium and albumin were examined in normal non-pregnant, normal pregnant and pre-eclamptic Nigerian women. Mean arterial pressure showed a positive correlation with age in non-pregnant subjects, but not in normal pregnant or pre-eclamptic women. There was no significant correlation of mean arterial pressure with parity, plasma sodium or albumin in any of the three groups. A weak positive correlation was found between mean arterial pressure and plasma osmolarity in non-pregnant women and, although this was absent in normal pregnancy, it reappeared as a significant negative correlation in pre-eclampsia. These observations were considered, with special reference to osmotic aspects of the changes involved, and biophysical aspects of oedema are discussed. It is suggested that the osmotic properties of interstitial fluid albumin play a key role in the development of both physiological and pathological oedema in pregnancy.

Pregnancy and Nelson's syndrome. Two case reports.

We describe two patients with Nelson's syndrome in whom pregnancy progressed normally to spontaneous delivery of normal infants. One patient, who subsequently was found to have a basophil adenoma of the pituitary, developed diabetes insipidus in late pregnancy and the diabetes insipidus regressed spontaneously after delivery.

Precocious puberty associated with primary hypothyroidism in a mongol girl.

A mongol child suffereing from hypothyroidism who presented with precocious puberty is described. A presumptive diagnosis of idiopathic precocious puberty was first made and she was treated initially with medroxyprogesterone acetate, and later, with cyproterone acetate. The diagnosis of primary hypothyroidism was made late because of misleading results of protein bound iodine estimations. Subsequently, thyroid medication resulted in a prompt return to the normal range of the previously elevated levels of plasma gonadotrophins, thyroid stimulating hormone and plasma and urinary oestrogens, but the serum prolactin remained elevated for several months after therapy was begun.

Plasma solute concentrations during gonadotrophin-induced ovulation.

The effects of ovulation induction on some plasma solute concentrations were investigated serially in eleven women, nine of whom conceived in that cycle. Increasing oestrogen output during the follicular phase was associated with decreasing levels of osmolality, urea, total protein and the albumin free protein fraction. Smaller decreases in the concentrations of sodium, potassium, chloride, carbon dioxide combining power (CO2CP) and albumin were not statistically significant. The luteal phase was marked by a rise in osmolality and a fall in CO2CP but no other significant changes. Levels of osmolality, sodium and potassium fell in early pregnancy when oestrogen output was further increased. These results appear consistent with an oestrogen induced expansion of the extracellular fluid compartment by retention of water in excess of solute, which might also account for the similar changes in pregnancy.

Haematological changes during ovulation-induction by gonadotrophins.

The oestrogen response to ovulation-induction by gonadotrophins initiates a preovulation rise in total leucocytes and promotes fluid retention. In consequence of the latter, cyclic changes occur in blood haemoglobin and the haematocrit. The level of oestrone excretion in the follicular phase of induced cycles indicates that multiple follicular development probably occurs, and this also appears to affect the luteal phase. It seems likely, therefore, that the data present a rather exaggerated picture of the situation which obtains in normal menstrual cycles.

Meteorological relations of eclampsia in Lagos, Nigeria.

A retrospective study of the meteorological relations of eclampsia in Lagos, Nigeria supports other observations that the incidence of this disease varies significantly with the weather. Protective action by arid conditions is consistent with the known effect of dehydration on convulsions of differing aetiologies and is attributable to increased pulmonary transpirational water loss. Exacerbation of eclampsia by cool, humid conditions may therefore reflect excessive water retention, due partly to suppressed pulmonary transpiration and partly to kidney malfunction in those women.