R. J. Pepperell

Treatment of Recurrent Aborters by Immunization With Paternal Cells—Controlled Trial

ABSTRACT: A paired sequential trial was undertaken to establish whether paternal mononuclear cells improved the prognosis in couples with recurrent abortions. For this purpose, 107‐108 cells obtained from the blood of partners were injected intravenously, subcutaneously, and intra‐dermally into women who had had three or more consecutive miscarriages with the same partner. Control women were given normal saline, injected in the same manner. The result of the sequential analysis showed that there was no significant beneficial effect of the cells compared to control. The overall success rate was 70% (32/46 couples). The success rate in patients given cells was 62% (13/21), while in those given saline it was 76% (19/25). While the overall success rate in this study compares with a number of other studies, we find an equally high success rate with non‐immunized patients. We conclude that the value of immunization for the prevention of recurrent miscarriage has not been established.

AN UNEXPECTEDLY HIGH RATE OF ECTOPIC PREGNANCY FOLLOWING THE INDUCTION OF OVULATION WITH HUMAN PITUITARY AND CHORIONIC GONADOTROPHIN

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).

Unexplained infertility: a review

Summary. When investigations fail to reveal a cause for infertility, treatment must then be based on possible, but unproven, causes, and since there is a high spontaneous pregnancy rate in unexplained infertility the effect of any treatment is difficult to assess. Such treatment has included correction of anatomical variants such as uterine retroversion and the use of hormonal manipulation during the follicular and luteal phases of the menstrual cycle. Ovum entrapment, occult spontaneous abortion and faults in sperm fertilizing capacity have all been implicated, and it is likely that immunological factors play a substantial role in unexplained infertility. Evidence does not support the use of bromocriptine in the absence of hyperprolactinaemia. Successful treatment by intrauterine insemination is unlikely if there are circulating anti‐sperm antibodies in the partner. Improving cervical mucus by treatment with oestrogens and clearing infections with antibiotics may have a modest place but it is very difficult to show that these treatments have more than a placebo effect. Endometriosis is often missed and the possibility of it having developed after initial investigation warrants repeat laparoscopy after 2 years. Three approaches are currently acceptable in the management of the couple with unexplained infertility: await spontaneous pregnancy, the empirical use of clomiphene and in‐vitro fertilization.

Cytoplasmic steroid receptors in ovarian tumours

Summary. Cytoplasmic oestrogen receptors were measured in 40 primary and four secondary ovarian tumours; of these, 43 tumours were also analysed for cytoplasmic progesterone receptors and 34 tumours for cytoplasmic androgen receptors. Serous tumours were significantly more likely to be oestrogen‐receptor positive than mucinous tumours, but the incidence of positive progesterone and androgen receptors was similar in serous, mucinous and endometrioid tumours. The mean oestrogen receptor content of serous tumours was significantly higher than that of endometrioid tumours. Well‐differentiated epithelial tumours were significantly more likely to be oestrogen‐receptor and progesterone‐receptor positive than less differentiated epithelial tumours. Two granulosa cell tumours were oestrogen‐receptor positive and one of these was also progesteronereceptor and androgen‐receptor positive. Four normal óvaries were also analysed for receptor content and two were found to be androgen‐receptor positive. The presence of cytoplasmic receptors in ovarian tumours may explain their reported response to endocrine therapy.

Rotational delivery of the fetus: Kielland's forceps and two other methods compared

Summary. A retrospective comparison was undertaken of 552 cases in which Kiellands forceps were used for rotation and delivery, 95 cases in which other forceps were used for rotation and delivery, and 160 cases in which manual rotation and forceps were used. There was no significant difference in maternal or fetal morbidity between the three groups, regardless of whether the indication for delivery was delay in the second stage of labour or fetal distress. When Kiellands forceps were used by junior staff, significantly more vaginal and cervical lacerations and primary postpartum haemorrhage occurred, but there was no increase in fetal morbidity.

THE RELATION BETWEEN MATERNAL SERUM ALPHA-FETOPROTEIN LEVELS AND FETOMATERNAL HAEMORRHAGE

Spontaneous fetomaternal haemorrhage at 14 to 20 weeks gestation resulted in raised serum alpha‐fetoprotein (AFP) levels in 13 of 150 patients attending a genetic counselling clinic. In all 13 patients, the placenta was anterior or fundal in position. By allowing for a rise in serum AFP levels of 4 μg/l for each fetal cell seen in 30 high power fields (Kleihauer test), a 62·5 per cent reduction in the number of patients selected for amniocentesis because of raised serum AFP levels would have been achieved. The occurrence of fetomaternal haemorrhages at the time of amniocentesis can be detected by either the Kleihauer technique or the measurement of maternal serum AFP levels.

THE INVESTIGATION OF OVARIAN FUNCTION BY MEASUREMENT OF URINARY OESTROGEN AND PREGNANEDIOL EXCRETION

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.

SERUM PROLACTIN LEVELS AND THE VALUE OF BROMOCRIPTINE IN THE TREATMENT OF ANOVULATORY INFERTILITY

Basal serum levels of prolactin were measured in 37 infertile anovulatory patients who had failed to conceive on therapy with clomiphene citrate. Twenty of these patients, 16 of whom had galactorrhoea, had elevated basal serum prolactin values which were suppressed to normal or subnormal values during therapy with bromocriptine, the most commonly effective dose being 2·5 mg twice daily. Ovulation, as assessed by urinary oestrogen and pregnanediol measurements, was induced in 17 of these patients with pregnancy in 14. Ovarian responses short of defined criteria for ovulation were induced initially in eight patients, but these progressed to full ovulatory responses in five patients, either on the same or increased doses of bromocriptine. In all the patients who ovulated, the prolactin levels had been reduced below the mean value for normal women (10·6 ng‐ml). The three patients who failed to ovulate all had values higher than this at a dose of bromocriptine reaching 5·0 mg thrice daily. There seemed to be no value in increasing the dose of bromocriptine once ovulation had been achieved. Of the 17 patients with normal basal prolactin values, only one had an unequivocal response to bromocriptine with ovulation and conception, even though the prolactin values in the majority were suppressed to below normal.

Gynaecological disorders and risk factors in premenopausal women predisposing to osteoporosis. A review

Osteoporosis is a common disorder with onethird of women over 65 years of age having vertebral fractures and by extreme old age, onethird of women having sustained a hip fracture (Riggs & Melton 1986~). Morbidity, mortality and costs of health care make osteoporosis a serious public health problem (Holbrook et al. 1984). The prevention of bone loss in perimenopausal women is an important aim in the prevention of fractures as there is no established safe and effective method of replacing bone already lost in elderly persons. There is no single cause of osteoporosis. Many diseases, as well as nutritional, social and environmental factors, influence bone mass in premenopausal women. This review summarizes the effects of important gynaecological disorders and environmental factors that may affect bone mass of women both before and after the menopause. We emphasize the role these factors may play in predisposing to osteoporosis and fractures in later life. Osteoporosis secondary to medical disorders such as hyperthyroidism, hyperparathyroidism, Cushing’s diseasc, rheumatoid arthritis and gastrectomy will not be considered.

Home monitoring of gonadotropin ovulation induction using the Ovarian Monitor

The safe use of gonadotropins relies on close hormonal and/or ultrasound monitoring to assess the response to treatment, requiring multiple hospital visits. Home monitoring with the Ovarian Monitor (St. Michael Research Foundation, Macleod, Victoria, Australia) minimizes hospital visits and overcomes many of the logistic difficulties associated with gonadotropin use. It utilizes a system of homogenous enzyme immunoassay using lysozyme conjugates to measure quantitatively either urinary estrone-3 or pregnanediol-3-glucuronide. Results obtained by 24 patients in 57 cycles using the Ovarian Monitor at home correlate closely with results obtained in the laboratory (estrone-3-glucuronide r = 0.955; pregnanediol-3-glucuronide r = 0.958). Cycle outcomes (ovulation, 74%/cycle; clinical pregnancy, 30%/cycle; multiple pregnancy, 13%/pregnancy; hyperstimulation, 11%/cycle) are no different from those achieved in laboratory-monitored patients. Home monitoring can be as safe and effective as laboratory monitoring, offers significant social benefits, and improves access to this form of therapy.