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Notes: Six tubal ectopic pregnancies occurred in a series of 193 pregnancies following ovulation induced with human pituitary gonadotrophin (hPG) and human chorionic gonadotrophin (hCG). The ectopic pregnancy rate of 3.1 per cent is higher than quoted incidences in the general population and occurred in the absence of predisposing factors. There was an association between ectopic pregnancy and elevated urinary oestrogen excretion in the peri-ovulatory phases of the induced ovulatory cycles. A urinary oestrogen excretion of greater than 200 μg/24 hours on day 0 (the day after hCG was given) was associated with a 10 per cent chance of ectopic pregnancy (P 〈0.05).

Notes: The lecithin/sphingomyelin (L/S) ratio, palmitic acid concentration and palmitic to stearic acid (P/S) ratio were estimated on samples of amniotic fluid obtained from 66 patients with diabetes. These were compared with similar estimates on amniotic fluid obtained from 127 non-diabetic patients. At 35 to 40 weeks, significant differences were observed between the L/S ratio and palmitic acid concentration in diabetics and non-diabetics, whereas the P/S ratio was similar in the two groups. The amniotic fluid L/S ratio, palmitic acid concentration, and P/S ratio were estimated on amniotic fluid obtained from 20 diabetic patients within 48 hours of induction, and the clinical outcome of the newborn infant was used to assess the predictive value of the three parameters. In 19 out of the 20 diabetics the P/S ratio correctly predicted fetal lung maturity, whereas the palmitic acid concentration was correct in 12 patients and the L/S ratio in only 10 patients.

Notes: Urinary oestrogen and pregnanediol excretion in 102 women who had a curettage for postmenopausal bleeding was correlated with the histological appearance of the endometrium, with age and with weight, and were compared with the values obtained in 42 normal postmenopausal women. The 36 patients with proliferative and hyperplastic endometrium and the 16 patients with endometrial carcinoma had significantly higher oestrogen excretion than the controls. The 27 patients with atrophic endometrium had only slightly higher mean oestrogen values than the controls. Twenty-three patients had taken hormones and the 20 patients who bled during treatment had the same urinary hormone values as the controls (excluding three patients with ovarian and/or endometrial carcinoma). The ovaries were examined in 37 patients who had a total hysterectomy and bilateral salpingo-oophorectomy. Significantly higher oestrogen values were found in those patients with ovarian tumours in which the stroma showed hyperplasia. When an ovarian tumour was associated with normal stroma or when the ovary showed cortical stromal hyperplasia without a tumour, urinary hormone values were normal. Oestrogen excretion and age were not related, but a correlation was found between oestrogen excretion and body weight.

Notes: Urinary oestrogen and pregnanediol excretion were measured before and after hysterectomy and bilateral salpingo-oophorectomy in 26 postmenopausal women with adenocarcinoma of the endometrium, 10 postmenopausal women with mixed adenosquamous carcinoma and 11 postmenopausal women with atypical hyperplasia (the patient groups). The results were compared with the values obtained in 22 active postmenopausal women, 20 hospitalized postmenopausal women and 18 women who had been subjected to hysterectomy and bilateral salpingo-oophorectomy for cancer of the cervix (the control groups). The ovaries and Fallopian tubes obtained at operation were examined for evidence of current or past excessive oestrogen production. Preoperative oestrogen values were higher in the patient groups than in the controls and the elevated values persisted after oophorectomy. The implications of these findings are discussed.

Notes: Serum prolactin levels and urinary oestrogen and pregnanediol excretion were measured during early pregnancy in 12 hyperprolactinaemic subjects who became pregnant during treatment with bromocriptine. Prolactin levels were suppressed below normal whilst taking the bromocriptine, but rose significantly when this drug was stopped and by eight weeks of gestation reached values significantly higher than those observed in normal pregnancy. Further increases in prolactin levels were, however, not observed. Urinary oestrogen and pregnanediol excretion was initially normal but, following cessation of bromocriptine, urinary pregnanediol excretion decreased and was significantly less than normal at 11 to 14 weeks gestation. These results suggest that elevated prolactin levels affect corpus luteum function of early pregnancy. Because the effect is maintained until at least 14 weeks gestation, prolactin may also affect progesterone production by the placenta.

Notes: Urinary oestrogen and pregnanediol excretion was measured daily (“daily monitoring”) for a complete cycle in 20 normally menstruating women, in one patient with an anovulatory cycle and for 28 days in a patient with secondary amenorrhoea. The measurements were also performed on urine specimens collected at weekly intervals for 4 to 6 weeks (“weekly tracking”) from 506 patients with evidence of abnormal ovarian function. These included 9 patients with primary amenorrhoea, 132 patients with secondary amenorrhoea, 138 patients with oligomenorrhoea and 227 patients with evidence of ovarian dysfunction and cycle lengths of 25 to 42 days. The results were subjected to statistical analysis. In the normal cycles, ovulation could be identified on the criteria of a rising pregnanediol value reaching or exceeding 2.0 mg. per 24 hours for a period of 7 days or more. Valid conclusions on the overall mean oestrogen and pregnanediol values for a complete cycle could be made from the results of weekly tracking, irrespective of which day the tracking commenced. Correlations were obtained by comparing the mean and maximum urinary oestrogen values and the variability of the values with the evidence of ovarian function indicated by the clinical classifications of the patients, the duration of the disorders and the subsequent occurrence of uterine bleeding. Mean oestrogen values of 10μ g. per 24 hours or less were associated with lack of ovarian function. For values higher than this a discriminant function based on both the mean oestrogen value and the variability of the oestrogen values was useful in predicting onset of spontaneous menstruation. A single urine specimen collected 4 to 8 days before onset of menstruation showing a raised pregnanediol value of 2.0mg. per 24 hours or more provided a valid test for ovulation in women with regular cycles, and a single urine specimen giving an oestrogen value of 10 pg. per 24 hours or less gave a valid indication of absent ovarian function in women with amenorrhoea for two years or more. In all other circumstances serial sampling at weekly intervals provided a valid assessment of ovarian activity. Application of these principles allows the greatest amount of information on ovarian function to be obtained with the greatest economy of effort.

Notes: The results of 201 24-hour urinary oestriol estimations in 50 twin pregnancies are presented. The 10th, 50th and 90th centiles were approximately 1.7 times higher than those for singleton pregnancies, reflecting the combined weights of the two fetuses. In general, the oestriol values were not low before or after intrauterine death of one fetus or in pregnancies with intrauterine growth retardation. The trends in serial oestriol values were of more relevance in assessing fetal jeopardy than grading the values as normal or low.

Notes: Twelve anovulatory patients with normal serum prolactin values and six with elevated values were treated with bromocriptine and the effects on serum prolactin, FSH and LH levels were recorded. Ovulation resulted in one patient who had normal prolactin values and in all six who had raised values. No patient with normal basal prolactin values showed an increase in serum FSH during therapy with bromocriptine, whereas 5 of the 6 patients with elevated values showed significant increases. Similar results were obtained for LH. Although these differences were highly significant (P〈0·005) the majority of the serum FSH and LH values remained within the normal ranges. Five patients with normal basal prolactin values and one with elevated values were also treated with human pituitary gonadotrophin (HPG). An increase in ovarian responsiveness to HPG during therapy with bromocriptine was recorded in the one patient with initially elevated prolactin values. It was concluded that bromocriptine acts by allowing FSH to rise above threshold requirements for follicular stimulation.

Notes: Fifty-five patients admitted to hospital with the diagnosis of threatened abortion were assessed by means of urinary oestrogen, pregnanediol and chorionic gonadotrophin assays and by vaginal cytology. Oestrogen excretion was abnormally low (below the first percentile for the period of gestation) in 22 patients all of whom aborted, usually within a week of the measurement. Twenty-two of the 33 patients with oestrogen values in the normal pregnancy range had pregnancies which continued and resulted in surviving infants. Eleven patients with normal oestrogen values subsequently aborted. These abortions occurred more than one week after the original assessment and usually in the second trimester. Pregnanediol measure ments provided comparable information. In patients who aborted, vaginal cytology and initial chorionic gonadotrophin levels were less useful investigations.

Notes: Forty-one patients with a diagnosis of possible hydatidiform mole were studied by HCG, oestrogen and pregnanediol determinations performed on 24-hour collections of urine. The results were compared with those obtained in a control series involving 5000 HCG analyses, 679 oestrogen analyses and 1080 pregnanediol analyses performed over the relevant period of gestation in single pregnancies which produced surviving infants. Of the 17 patients who were shown to have a hydatidiform mole, 8 (47 per cent) had high HCG levels, 5 (29 per cent) had oestrogen levels below the first percentile for the control series and 5 of 13 patients had low pregnanediol levels (38 per cent). Five of the nine patients with molar pregnancies associated with normal HCG excretion had oestrogen excretion below the first percentile and one of the remaining four with normal oestrogen values had non-pregnancy levels of pregnanediol. Thus the diagnosis of an abnormal pregnancy could be made in 14 of the 17 molar pregnancies studied (82 per cent). Two of the three exceptions had a fetus co-existent with the mole. There were no viable pregnancies when the oestrogen and pregnanediol values were below the first percentile. Oestrogen and/or pregnanediol values in the range consistent with multiple pregnancy were found in four patients with molar pregnancies. In the molar pregnancies there was a correlation between the levels of HCG and the levels of oestrogens and pregnanediol excreted. After evacuation of the mole, the levels of oestrogens and pregnanediol remained elevated for up to three weeks in approximately half of the patients, whereas the HCG levels fell immediately. These findings support the view that in molar pregnancies, levels of oestrogens above 300 μg. per 24 hours and of pregnanediol above 10 mg. per 24 hours are derived mainly from the stimulation of theca lutein cysts in the ovaries.