British Journal of Obstetrics and Gynaecology October 1976. Vol. 83. pp 828-830

PAPERS PRESENTED AT THE BLAIR BELL RESEARCH SOCIETY ON 5TH APRIL, 1976 AT THE ROYAL COLLEGE

OF OBSTETRICIANS AND GYNAECOLOGISTS

‘POST-PILL’ AMENORRHOEA- FACT OR FANCY?

H. S. JACOBS M. G. R. HULL

M. A, F. MURRAY

S. FRANKS Department of Obstetrics and Gynaecology

St Mary’s Hospital Medical School, London

THE relationship of functional diagnosis and previous oral contraceptive therapy was studied in 95 women who presented consecutively with secondary amenorrhoea. The functional cate- gories of amenorrhoea recognized were : primary ovarian failure (19 per cent); hyperprolac- tinaemia (1 9 per cent) ; hypothalamic disorders due to defective negative feedback (31 per cent); hypothalamic disorders due to defective cycle initiation (1 5 per cent) ; hypothalamic disorders of uncertain type (10 per cent); polycystic ovarian disease (6 per cent). The majority of patients with defective negative feedback had either partially recovered anorexia nervosa, or some other readily identifiable psychiatric disturbance. Fifty-one of the 95 patients had used the oral contraceptive and 37 complained of amenor- rhoea occurring immediately after its dis- continuation; 18 of these patients, however, had also had episodes of amenorrhoea before starting contraceptive therapy. Even when these cases were excluded, there were patients with amenor- rhoea following the use of oral contraceptives in all of the diagnostic categories. Moreover, in these groups the frequency of amenorrhoea after oral contraceptive therapy was unrelated to the frequency of oral contraceptive usage. However, the proportion of former oral contraceptive users developing amenorrhoea was highest in the groups with the disorders which tend to be

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persistent (ovarian failure, hyperprolactinaemia and anorexia nervosa). These data indicate that amenorrhoea after the use of oral contraceptives is not associated with or due to any single specific functional disorder. There is no doubt about the need for full investigation of all patients with amenorrhoea, irrespective of their previous contraceptive history.

A STUDY OF GONADOTROPHIN RELEASE IN WOMEN WITH

HYPERPROLACTINAEMIA AND AMENORRHOEA

M. R. GLASS R. W. SHAW

W. R. BUTT Birmingham and Midland Hospital for Women

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AN amplification of the LH response to LH-RH (100 pg) in 4 out of 10 women with hyper- prolactinaemic amenorrhoea and of the FSH response to LH-RH in 1 out of 10 occurred 44 hours after the administration of oestradiol benzoate. The average amount of LH released before and after oestrogen did not change, and there was a significant decrease in the amount of FSH released. There was no corre- lation between the amount of LH released and the serum oestradiol concentration at the time of the LH-RH tests, and there was a negative correlation between the FSH released and the oestradiol concentration (r = 0.507; p<O.O5). These results contrast with those obtained in normal subjects in the follicular phase of the cycle when there is a positive correlation (p<O.OOl) between the oestrogen levels and the amount of LH and FSH released. The presence of an amplification of LH response to LH-RH

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by oestrogen in 4 subjects correlated with the presence of ovulatory responses to clomiphene and previously observed rises in circulating LH concentrations 48 to 96 hours following oestradiol benzoate administration. These results indicate that in hyperprolactinaemia failure of ovulation may be related to failure of positive feedback of oestrogen. Oestrogen negative feedback is normal and unopposed and this may explain the inadequate follicular develop- ment and consequent amenorrhoea.

Mean serum gonadotrophin concentrations (both basal and after LH-RH) were normal in 42 patients, but below normal in 4 patients who had had pituitary ablation. Galactorrhoea occurred in 38 per cent of patients. Of the 30 patients treated with clomiphene, 24 failed to ovulate. There were 17 patients who were treated with bromocriptine: 14 ovulated and 8 of these became piegnant within 3 cycles.

AMNIOTIC FLUID PROTEINS IN EARLY AND LATE PREGNANCY

CLINICAL AND ENDOCRINE FINDINGS BY

IN 50,WOMEN WITH D. BURNETT HYPERPROLACTINAEMIC B. V. LEWIS

AMENORRHOEA s. M. WOOD BY A. R. BRADWELL

S. FRANKS S. J. STEELE

J. D. N. NABARRO Middlesex Hospital, London

M. A. F. MURRAY M. G. R. HULL

H. S. JACOBS St Mary’s Hospital Medical School, London

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THE clinical, radiological and endocrine findings in 50 women with hyperprolactinaemia and amenorrhoea were presented. There were 15 patients with radiological evidence of a pituitary tumour and a further 6 patients were studied after pituitary ablation. The remaining 29 women with hyperprolactinaemia had normal pituitary fossa X-rays. Basal serum prolactin concentrations were generally higher in the group with untreated pituitary tumours than in those patients with normal X-rays. The levels after pituitary ablation ranged from slightly elevated to very high. Serum oestradiol-17P concentrations were low in all patients and 29 of 31 patients tested showed no withdrawal bleeding after treatment with a progestogen.

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J. W. STUDD Birmingham Maternity Hospital and Watfovd

General Hospital

PAIRED amniotic fluid and maternal serum samples were collected from 12 patients in early pregnancy (14 to 19 weeks gestation), and 24 patients in late pregnancy (35 to 40 weeks gestation) of which 12 were uncomplicated and 12 had pre-eclampsia). Cord blood was also collected from each patient with an uncompli- cated late pregnancy. The concentrations of 1 1 proteins were estimated in the specimens by quantitative immunoelectrophoresis. The amniotic fluid/serum concentration ratio was calculated for the 11 proteins in each subject (a measure of permeability of the blood/ amniotic barrier to the protein). In late pregnancy, the amniotic fluidlmaternal serum ratios of the proteins gave a significant linear correlation with protein Stokes radius (r = 0.95) but amniotic fluidlfetal serum ratios did not (r = 0.02 to 0.52). The plasma proteins in amniotic fluid of the late pregnancy therefore appear to originate in the maternal circulation and to filter across the blood/amniotic fluid barrier depending upon their size. In early pregnancy the amniotic fluid/serum ratios gave

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significant correlation with Stokes radius, but the correlations were less significant than in late pregnancy. This may be due to the fetus contributing some protein material to the amniotic fluid in early pregnancy. A significant difference was observed between the mean slopes of the regression lines of amniotic fluid/ serum ratios against protein Stokes radii for normal late pregnancies and those with pre- eclampsia (p<O-OI). This signifies a relative increase in permeability of the fetal membranes to smaller proteins in pre-eclampsia.

CHROMOSOMAL ANOMALIES ASSOCIATED WITH MOUSE FERTILIZATION IN VlTRO

LYNN R. FRASER Clinical Research Centre, Harrow

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ALTHOUGH particular interest has been generated by the proposed use of the fertilization in vitro technique to alleviate certain types of infertility in humans, care must be taken to minimize the risk of an increased incidence of anomalies. Employing a successful in vitro system, we have begun to examine the chromosomes of mouse embryos fertilized in vitro. We found a highly significant increase in triploidy in these embryos (22/172, 12-8 per cent) compared with naturally ovulated control embryos (5/184, 2.7 per cent). This triploidy could be due to either digyny (retention of the second polar body) or diandry (either two sperm or one diploid sperm).

THE HIGH RISK MALE IN THE AETIOLOGY OF CERVICAL CARCTNOMA

A. SINGER University of Shefield

BEVAN REID University of Sydney, Australia

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EPIDEM~OLOGICAL evidence suggests that squamous cell carcinoma of the cervix results from the interaction of venearally transmitted substances between predisposed males and females. This association can be expressed at the cellular and molecular levels of organization in terms of the following hypothesis. Squamous cervical metaplasia establishes a population of susceptible cells by virtue of their surface coat which is unusually endowed with deoxy- ribonucleoprotein filaments. Certain males are considered to be more likely than others to transmit this disease to their spouse; social class and certain occupations characterizing this group. The agent transmitted may be an arginine-rich histone which is produced in varying amounts during the degradation of the sperm. The histone is released from an association with the D N A of the heterochromatin fraction of the sperm head. Free on the cervix, the histone may draw excessive amounts of D N A from the nucleus of the susceptible cells to the cell surface where it endows these cells with potentially neoplastic properties. The same oncogenic mechanism may be proposed for viiuses of the herpes type, but reasons were given for believing that the gamete-associated histones were of greater importance.