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Pregnancy is proposed to be a Th2 phenomenon, where Th2 cytokines inhibit Th1 responses to improve foetal survival. The importance of interleukin-10 (IL-10), an immunomodulatory cytokine produced by Th2 cells, in the maintenance of normal pregnancy is becoming increasingly apparent. In a longitudinal case-control study, the physiological effect of pregnancy on plasma IL-10 was investigated. The plasma concentration of IL-10 was determined using an ELISA technique in 99 pregnant women sampled at 12, 20 and 35 weeks of gestation, 38 non-pregnant control subjects sampled in parallel and in a subgroup of women sampled at 3 days post-partum (n, pregnant 21, non-pregnant 21). Plasma IL-10 was significantly higher in pregnant women at 12, 20 and 35 weeks of gestation (p<0.05, p<0.01 and p<0.0001, respectively), and in mothers post-delivery (p<0.01) when compared to non-pregnant control subjects. Furthermore, there was no significant effect of gestational time on IL-10 concentration. Results from the current study suggest that elevated IL-10 is a physiological consequence of normal healthy pregnancy. These findings help clarify previous conflicting results and establish a range for plasma levels of IL-10 in normal healthy pregnancy.

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OBJECTIVE: To investigate soluble P-selectin (sP-selectin) levels and platelet parameters in normal pregnant women compared with non-pregnant control subjects. DESIGN: A longitudinal case-control study. SETTING: Obstetric outpatient clinic in the Jubilee Maternity Hospital, Belfast. POPULATION: One hundred and twenty normal pregnant women and 41 non-pregnant age-matched control subjects. METHODS: The plasma concentration of sP-selectin in pregnant women sampled at 12, 20 and 35 weeks of gestation, and, in a subgroup at three days postpartum, and non-pregnant controls sampled in parallel, was determined using a commercial quantitative sandwich immunoassay kit. Platelet parameters on each blood sample were also recorded using a SYSMEX SE 9500 analyser. MAIN OUTCOME MEASURES: Plasma sP-selectin as a measure of platelet activation in normal pregnancy. RESULTS: Soluble P-selectin was significantly higher in pregnant women than in non-pregnant control subjects at 20 and 35 weeks of gestation, (P < 0.01, and P < 0.001, respectively). Correlation analyses showed positive correlation between sP-selectin and platelet count in pregnant women at 20 and 35 weeks of gestation (r = 0.247, P < 0.05 and r = 0.360, P < 0.001, respectively). Soluble P-selectin concentration per platelet was also significantly higher in pregnant women than in non-pregnant control subjects at 20 and 35 weeks of gestation (P < 0.001). CONCLUSIONS: Our results show that sP-selectin concentration is significantly higher in the second and third trimester of pregnancy when compared with non-pregnant control subjects sampled in parallel. This finding clarifies previous conflicting results on platelet activation in normal pregnancy, and is in agreement with those earlier studies which reported, using other methods, increased platelet activation in normal pregnancy.

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Pregnancy is often referred to as a hypercoagulable state due to changes in the haemostatic system. Tissue factor (TF) is the initiator of blood clotting in vivo. The effect of pregnancy on monocyte TF expression was determined in a longitudinal case control study (89 pregnant, 39 non-pregnant). Using whole blood flow cytometry and CD14 as a monocyte marker, TF expression was measured on all CD14 positive, CD14Bright and CD14Dim cells. TF expression was significantly lower in pregnant women than in non-pregnant control subjects, on all CD14 positive cells at 20 and 35 weeks, on CD14Bright cells at 12 and 35 weeks and on CD14Dim cells at 20 weeks. Additionally, we report that a higher percentage of CD14Dim than CD14Bright cells express TF. These results suggest that, in order to maintain homeostasis in haemostasis in an otherwise hypercoagulable state, monocyte TF expression is reduced during normal pregnancy.

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OBJECTIVE: To evaluate the safety and efficacy of thermal balloon therapy for menorrhagia. DESIGN: Prospective, observational study. SETTING: Fifteen centres in Canada and Europe. POPULATION: Two hundred and ninety-six eligible women for whom follow up data were available for three months or more. Eligible women included those for whom further fertility was not a concern, were not postmenopausal, suffered from intractable menorrhagia, had a normal uterine cavity, and who were fully informed regarding the investigational nature of uterine thermal balloon therapy. METHODS: Three hundred and twenty-one procedures of balloon endometrial ablation were performed using the same protocol between June 1994 and August 1996. Exclusion criteria included structural uterine abnormality or (pre) malignant lesions. Treatment entailed controlled heating of fluid in an intrauterine balloon. General anaesthesia was employed in the 61% of procedures while local anaesthesia with or without sedation was used in 39% of cases. ANALYSIS: Follow up data at 3 and/or 6, and/or 12 months were required for inclusion in the analysis. A paired t test, Wilcoxon signed-ranks test, and multiple and logistic regression analyses were used to evaluate the changes in bleeding and dysmenorrhoea patterns, and possible confounding variables, respectively. Success was defined as the subjective reduction of menses to eumenorrhoea or less. RESULTS: No intra-operative complications occurred, and post-operative morbidity was minimal. Success of the procedure was constant over the year (range 88%-91%). Treatment led to a significant decrease in the duration of menstrual flow and severity of pain (P < 0.0001). Increasing age, higher balloon pressure, smaller uterine cavity, and a lesser degree of pre-procedure menorrhagia were associated with significantly improved results. Pre-treatment with gonadotrophin releasing hormone agonists increased amenorrhoea and spotting rates (P = 0.03), but was only used in 5% of cases. CONCLUSION: Thermal balloon endometrial ablation appears to be safe, as well as effective in properly selected women with menorrhagia and is potentially an outpatient procedure.

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We report the results of a pilot study conducted to compare the efficacy of oral prostaglandin E2 versus intravenous oxytocin in inducing labour after lower amniotomy in 20 primigravid patients at term. The results suggest no significant differences in the performance of each group for the induction to delivery interval, the mode of delivery, the Apgar score at five minutes or for third stage abnormalities. However, the use of oral PGE2 allows the patient unrestricted mobility and avoids the discomfort of i.v. infusions.

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The objective structured clinical examination (OSCE) now has an established place in the assessment of the medical undergraduate. While much has been written about the reliability of the OSCE, empirical work on the determination of the passing score which represents competence on the OSCE is rarely encountered. If the OSCE is to play its role in the 'high stakes' testing of clinical competence, it is important that this passing score be set reliably and defensibly. This article illustrates how a two-session modified Angoff standard-setting procedure is used to set the passing score on a 14 station Obstetrics and Gynaecology OSCE used to assess final year students at The Queen's University of Belfast. The Angoff methodology harnesses the professional judgement of expert judges to establish defensible standards. Four university teachers, five non-academic consultants and six junior clinical staff took part in a two-session Angoff standard-setting procedure. In the first session, the judges (individually and in silence) used their professional judgement to estimate the score which a minimally competent final year obstetrics and gynaecology student should achieve on each tested element of the OSCE. In the second session they revised their session 1 judgements in the light of the OSCE scores of real students and the opportunity for structured discussion. The passing score for the OSCE is reported together with the statistical measures which assure its reliability.

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OBJECTIVE: To assess the outcome of pregnancy following assisted conception. DESIGN: Cohort descriptive study. SETTING: Unit of Reproductive Medicine, Ninewells Hospital and Medical School. SUBJECTS: One hundred and forty-eight consecutive assisted conceptions. MAIN OUTCOME MEASURES: Patient characteristics and outcome of pregnancy. RESULTS: Seventy-nine percent of mothers were aged between 26 and 35 years (mean 31.4). The main causes of infertility were tubal (48%), unexplained (35%), anovulatory (8%) and male factor (8%). Primary infertility accounted for 61% of cases and 82% of pregnancies occurred within 3 treatment cycles. Thirty-five (24%) pregnancies miscarried before 14 weeks and 7 (5%) between 15 and 24 weeks gestation. One hundred and three pregnancies resulted in 136 liveborn infants. There was one neonatal death. Thirty-five babies were admitted to SCBU. Antenatally, 13% of patients were admitted to hospital with hypertension and 8% with APH; 50% of multiple and 13% of singleton pregnancies were delivered prematurely, 68% following preterm labour. There were 28 sets of twins (four miscarried at less than 24 weeks) and four sets of triplets. Multiple pregnancy was not associated with cause of infertility, treatment, age or ovarian hyperstimulation syndrome. Seventy-eight per cent of singletons and 50% of multipara were delivered vaginally. CONCLUSIONS: Our data confirm the high incidence of pregnancy loss and preterm delivery associated with assisted conception once allowing for the high rate of multiple pregnancies. The effect of assisted conception programme on health services is discussed.

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OBJECTIVE: To compare and assess clinical competence among final year students in two British medical schools using a standardised objective structured clinical examination (OSCE) in obstetrics and gynaecology. DESIGN: A comparative study of an OSCE with stations designed to test student abilities in history-taking, physical examination, interpretation of data or results, interpersonal skills, practical procedures, as well as factual knowledge. SUBJECTS: Two groups of final year medical students from two British medical schools. METHODS: An OSCE of 26 stations. RESULTS: The standardised OSCE was simple to organise and conduct once the content had been decided. Analysis of the results revealed significant differences in mean marks between the two sets of students in six stations, and in eight stations the mean score was less than five for one or other sets of students. The reasons for the differences between the medical schools and the poor performance of the students at some stations were investigated and possible causative factors identified. CONCLUSIONS: We have shown that an OSCE is suitable for testing clinical competence of students within and across medical schools, is able to highlight differences in standards between institutions, and can identify areas where teaching methods and/or course content are deficient.

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OBJECTIVE: To determine age specific prevalence of HIV antibody, incidence of pregnancy, and likelihood of detection and correct assignment to risk category by antenatal screening of women known to be positive for HIV antibody, from 1984 to 1989. DESIGN: Retrospective analysis of reproductive history and risk behaviour of women positive for HIV antibody and prediction of detection by screening on the basis of blood group samples, Guthrie tests, and rubella tests. SETTING: City of Dundee, where the prevalence of HIV is high, since the appearance of HIV in 1984, predominantly among heterosexual intravenous drug users. PATIENTS: All (61) women known to be positive for HIV antibody who had had clinically indicated tests, for whom case notes were available for 60. MAIN OUTCOME MEASURES: Risk assessment according to case notes and reported to the laboratory, incidence of infection, geographical location, age, date of positive test result, and reproductive history. RESULTS: With 61 infected women the overall minimum prevalence among women within the city of Dundee was 0.67/1000 and 2.9/1000 among women in their third decade. Of the 60 women whose reproductive history was available, 35 had 57 pregnancies, 36 of which occurred after seroconversion was known to have taken place, representing 8.7% of the total number of affected pregnancies reported for the United Kingdom. If antenatal screening for HIV had been performed between 1984 and 1989 it could not have detected positivity for HIV antibody in 25 (42%) women who had no pregnancies during this time. Among the remaining 35 women, screening samples taken for blood grouping could have identified a maximum of 34 (57%), samples taken to check rubella susceptibility a maximum of 22 (37%), and blood spots on Guthrie cards a maximum of 19 (32%). Retesting would have occurred in 14 women 33 times with samples taken for blood grouping, but three and four women would have been tested twice using samples taken for rubella testing and Guthrie cards respectively. Anonymous screening would have been unable to determine risk category as a history of intravenous drug use was known in 47 (79%) women before testing but this was increased by a further 5 (8%) who admitted to it after the test result was known. CONCLUSION: Interpreting the results of antenatal screening programmes will be complex and will underestimate overall prevalence of HIV antibody among women; this will be exaggerated by strategies based on anonymous testing with Guthrie cards or on samples taken for rubella testing, which do not include women who have had an earlier loss of pregnancy. Only open testing with consent will permit satisfactory attribution to

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Two hundred ten treatment cycles of follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG) were completed in 49 patients with clomiphene citrate-resistant polycystic ovarian syndrome. The results from 68 cycles of daily intramuscular (IM) FSH and 41 cycles of IM hMG were compared. The ovulation rate, maximum serum estradiol (E2) levels achieved, and pregnancy rate were similar in both groups, but FSH resulted in significantly fewer follicles developing and hyperstimulation. The 68 cycles of daily IM FSH were further compared with the outcome of administering the FSH as an alternate-day IM injection in 70 cycles, and by subcutaneous pulsatile injection in 31 cycles. There were no differences in any of the parameters measured between daily and alternate-day FSH. Pulsatile FSH required a greater total dose over a longer period of time to achieve stimulation. It also produced fewer follicles, a lower maximum serum E2 level, and the lowest incidence of hyperstimulation. Twenty pregnancies resulted, of which 6 aborted in the first trimester; there was 1 set of twins and 13 singleton pregnancies. The cumulative pregnancy rate after 6 treatment cycles was 62%.

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High ovulation rates can be achieved in women with PCOS, using hMG or FSH to induce ovulation, but the pregnancy rate is lower than expected. To determine whether this might be due to premature luteinization, progesterone levels were measured in the follicular phase of 49 infertile women with PCOS treated with hMG or FSH. The ovulation rate was 88.6% overall and 20 patients conceived. Six pregnancies aborted within four weeks of ovulation. Premature luteinization occurred in 32% of treatment cycles, of which three resulted in conception, compared to 17 conceptions in the 68% of cycles not associated with premature luteinization (p = 0.06). Of the 17 conceptions not associated with premature luteinization, three aborted and 14 proceeded to term; all three conceptions associated with premature luteinization aborted (p = 0.01). These results indicate that premature luteinization in women with PCOS is common, and has a deleterious effect on the rate of conception, and may also be a causal factor in early pregnancy loss.

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The effectiveness of intramuscular follicle stimulating hormone (FSH) administered as daily or alternate-day injections to patients with polycystic ovarian disease (PCOD) who previously failed to ovulate on clomiphene citrate was compared. The study comprised 20 treatment cycles of daily FSH and 19 of alternate-day FSH in 12 patients. The overall ovulation rate per cycle was 78% and was similar for both groups. Nine out of 12 patients achieved a pregnancy, with twice as many occurring in the alternate-day group. It is concluded that alternate-day FSH therapy is as effective as daily FSH in achieving ovulation and pregnancies in patients with PCOD resistant to treatment with clomiphene citrate.

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Between 1970 and 1983, 519 pregnancies in 405 women with heart disease were managed at the Royal Maternity Hospital, Belfast, Northern Ireland, a rate of 1.3 per 100 deliveries. In 312 (60%) the heart disease was of rheumatic origin, in 161 (31%) congenital, and the remaining 46 (9%) were a miscellaneous group that included arrhythmias, ischaemic heart disease and cardiomyopathies. The New York Heart Association (NHYA) grading was no greater than 1-2 in 445 (86%) pregnancies antenatally. Three maternal deaths occurred, all in the group whose antenatal NYHA grade was 3-4. Heart failure was present in 96 (18%) pregnancies antenatally, and six others developed failure during labour or in the puerperium. Prophylactic antibiotics were not used routinely and infective endocarditis did not occur. The perinatal mortality rate was 19/1000, and the rate of congenital malformations was not raised in the reviewed group.

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Five patients with carefully defined polycystic ovarian disease (PCOS) were treated with pure follicle stimulating hormone (FSH) to induce ovulation. Serum levels of androstenedione and testosterone were measured daily and noted to rise dramatically, reaching a maximum at the time of ovulation. However, despite the rise in androgens, ovulation occurred in each case and three patients conceived. Contrary to the traditional concept, it is concluded that elevated androgen levels in patients with PCOS do not interfere with ovulation induction using pure FSH.

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