Gynaecological endoscopic evaluation of 4% icodextrin solution: a European, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery.

BACKGROUND: Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringer's solution (LRS). METHODS: Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS--75% myomectomy/25% endometriotic cysts; 170 Adept--79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related. CONCLUSIONS: The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

Development and implementation of a participative intervention to improve the psychosocial work environment and mental health in an acute care hospital.

OBJECTIVES: To describe the development and implementation phases of a participative intervention aimed at reducing four theory grounded and empirically supported adverse psychosocial work factors (high psychological demands, low decision latitude, low social support, and low reward), and their mental health effects. METHODS: The intervention was realised among 500 care providers in an acute care hospital. A prior risk evaluation was performed, using a quantitative approach, to determine the prevalence of adverse psychosocial work factors and of psychological distress in the hospital compared to an appropriate reference population. In addition, a qualitative approach included observation in the care units, interviews with key informants, and collaborative work with an intervention team (IT) including all stakeholders. RESULTS: The prior risk evaluation showed a high prevalence of adverse psychosocial factors and psychological distress among care providers compared to a representative sample of workers from the general population. Psychosocial variables at work associated with psychological distress in the prior risk evaluation were high psychological demands (prevalence ratio (PR) = 2.27), low social support from supervisors and co-workers (PR = 1.35), low reward (PR = 2.92), and effort-reward imbalance (PR = 2.65). These results showed the empirical relevance of an intervention on the four selected adverse psychosocial factors among care providers. Qualitative methods permitted the identification of 56 adverse conditions and of their solutions. Targets of intervention were related to team work and team spirit, staffing processes, work organisation, training, communication, and ergonomy. CONCLUSION: This study adds to the scarce literature describing the development and implementation of preventive intervention aimed at reducing psychosocial factors at work and their health effects. Even if adverse conditions in the psychosocial environment and solutions identified in this study may be specific to the healthcare sector, the intervention process used (participative problem solving) appears highly exportable to other work organisations.

Superoxide dismutase activity in human follicular fluid after controlled ovarian hyperstimulation in women undergoing in vitro fertilization.

OBJECTIVE: To determine the activity of superoxide dismutase (SOD) and the total protein concentration in human preovulatory ovarian follicular fluid (FF) in relation to corresponding serum levels and the fertilization capacity of oocytes. DESIGN: Prospective, observational study. SETTING: Academic-based center for reproductive medicine. PATIENT(S): Twenty-eight female partners of infertile couples, 13 of whom were smokers, undergoing controlled ovarian hyperstimulation for IVF. INTERVENTION(S): Blood and follicular fluid samples were collected 34-36 hours after hCG administration. MAIN OUTCOME MEASURE(S): Levels of SOD activity and total protein concentrations. RESULT(S): Superoxide dismutase activity was present in all the FF studied and mean levels were statistically significantly higher than in serum. Total protein concentrations in serum were statistically significantly correlated with corresponding concentrations in FF. There was no difference in SOD activity between smokers and nonsmokers. Total protein concentrations in FF were marginally and statistically significantly lower in nonsmokers. Follicular fluid from patients whose oocytes did not become fertilized had a statistically significantly higher level of SOD activity than that from patients whose oocytes did become fertilized. CONCLUSION(S): Superoxide dismutase activity is present in FF and is higher than in serum. The degree of SOD activity is variable and seems to be inversely related to the fertilization of oocytes.

Male infertility.

Infertility affects 13-18% of couples and growing evidence from clinical and epidemiological studies suggests an increasing incidence of male reproductive problems. The pathogenesis of male infertility can be reflected by defective spermatogenesis due to pituitary disorders, testicular cancer, germ cell aplasia, varicocele and environmental factors or to defective sperm transport due to congenital abnormalities or immunological and neurogenic factors. Recent studies suggest an increased incidence of genetic disorders related to male infertility which may affect different levels, interfering with germ cell generation and maturation or leading to the production of non-functional spermatozoa. The identification of genetic causes of male infertility raises the issue of the transmission of defects to the offspring, a situation that is becoming more important given the increasing use of intracytoplasmic sperm injection (ICSI), a procedure in which the natural selection of the spermatozoa is by-passed. Fertilization can occur in vitro using ejaculated, epididymal or testicular spermatozoa, either fresh or frozen-thawed, providing opportunities hitherto not possible for men to be genetic fathers.

Clinical evaluation of three different gonadotrophin-releasing hormone analogues in an IVF programme: a prospective study.

The efficacy and safety of short acting buserelin and nafarelin intranasal spray were compared to long acting leuprorelin depot intramuscular or subcutaneous injection in this prospective study of 157 women undergoing controlled ovarian hyperstimulation (COH) for in-vitro fertilisation (IVF). Patients were allocated to three groups to receive buserelin 150 microg nasal spray three times daily (Group B), nafarelin nasal spray 400 microg twice daily (Group N), or leuprorelin depot 3.75 mg once by intramuscular or subcutaneous injection (Group L) for pituitary desensitisation prior to commencing COH with human menopausal gonadotrophins (hMG) according to the Centre's protocol. The mean (+/-S.D.) age (years) (32.6+/-3.8: Group B, 32.1+/-3.3: Group N versus 32.1+/-3.3: Group L); mean (+/-S.D.) total dosage of hMG (ampoules) (37.5+/-16.1: Group B, 39.8+/-14.2: Group N versus 41.9+/-12.6: Group L) and mean daily dosage of hMG (ampoules) (3.1: Group B, 2.8: Group N versus 3.0: Group L) seen were not statistically significantly different. The duration between starting the different gonadotrophin-releasing hormone (GnRHa) and the beginning of the next menstrual period was also not seen to be statistically significantly different between the three groups (Group B: 10+/-5.5, Group N: 9.1+/-4.1 versus Group L: 8.2+/-3, days). The number of abandoned cycles was higher in Group L (17% versus 11.8%: Group B and 11.3%: Group N) but this difference did not reach statistical significance. The clinical pregnancy rates per oocyte retrieval and per embryo transfer procedure were respectively, 31.1, 35% in Group B, 12.8, 14% in Group N versus 20.5, 23.7 in Group L and were not seen to be statistically significantly different even when ongoing pregnancy rates were compared. Apart from a statistically significantly greater incidence of allergic nasal reactions in the nafarelin group (P=0.001), all other side-effects were not shown to be statistically significantly different between the three groups. We conclude that a single dose of leuprorelin depot can be considered to be as an equally effective alternative to multiple doses of buserelin or nafarelin for pituitary desensitisation in women undergoing COH for IVF.

Incidence and risk factors for injury in non-elite Australian Football.

This paper identifies the risk and protective factors for injury in non-elite Australian Football. Five hundred and thirty five non-elite Australian footballers completed a baseline questionnaire at the commencement of the 1997 preseason. Participants were telephoned each month during the 1997 and 1998 playing seasons to provide details of their exposure at training and games and any injury experiences in the previous four weeks. The incidence of injury in this study was 24 injuries per 1000 player hours. The risk factors for injury were identified as: not wearing sports-specific football boots (IRR 1.40, 95% CI 1.03-1.90); an existing back pathology (IRR 1.29, 95% CI 1.10-1.51); excessive foot pronation (IRR 1.29, 95% CI 1.07-1.56); and extroverted behaviour (IRR 1.01, 95% CI 1.00-1.03). Cooling down after training (IRR 0.95, 95% CI 0.90-0.99) and not being injured in the previous 12 months (IRR 0.73, 95% CI 0.61-0.88) were found to be protective against injury. This study found that there was a high risk of injury associated with playing Australian Football at a community level. Further research is required to gain an understanding of the mechanisms by which the identified risk factors influence injury risk in community level Australian Football.

Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography.

OBJECTIVE: To assess the performance of the sequential combination of serum CA 125 measurement and ultrasonography in screening for ovarian cancer. DESIGN: The serum CA 125 concentration of each subject was determined and those with a concentration > or = 30 U/ml were recalled for abdominal ultrasonography. If ultrasonography gave abnormal results surgical investigation was arranged. Volunteers were followed up by annual postal questionnaire. SETTING: General practice, occupational health departments, ovarian cancer screening clinic. SUBJECTS: 22,000 women volunteers who were postmenopausal and aged over 45 years. MAIN OUTCOME MEASURES: Apparent sensitivity, specificity, positive predictive value, years of cancer detected. RESULTS: 41 women had a positive screening result and were investigated surgically. 11 had ovarian cancer (true positive result) and 30 had other disorders or no abnormality (false positive result). Of the 21,959 volunteers with a negative screening result, eight subsequently presented clinically with ovarian cancer (false negative result) and 21,951 had not developed ovarian cancer during follow up (apparent true negative result). The screening protocol achieved a specificity of 99.9%, a positive predictive value of 26.8%, and an apparent sensitivity of 78.6% and 57.9% at one year and two year follow up respectively. The estimated number of years of cancer detected by the prevalence screen was 1.4 years. CONCLUSIONS: This screening protocol is highly specific for ovarian cancer and can detect a substantial proportion of cases at a preclinical stage. Further investigation is required to determine the effect of the screening protocol on the ratio of early to late stage disease detected and on mortality from ovarian cancer.

The value of serum levels of oestradiol, progesterone and beta-human chorionic gonadotrophin in the prediction of early pregnancy loss.

Serial serum levels of oestradiol, progesterone and the beta-subunit of human chorionic gonadotrophin (beta-HCG) had been performed in 674 cycles in women conceiving a singleton pregnancy, either spontaneously or as a result of assisted conception. To determine the value of these estimations in the prediction of early pregnancy loss, frequency distribution curves and receiver operating characteristic curves were derived for the respective hormones measured at weeks 4-7 of gestation and expressed as multiples of the median (MoM) values in pregnancies occurring both with and without ovarian stimulation. A cut-off level of beta-HCG less than 0.5 MoM gave a sensitivity of 68% with an odds ratio of 4.0 at 7 weeks in unstimulated cycles in the prediction of pregnancy failure. A cut-off of 0.8 MoM for progesterone gave a sensitivity of 59% and an odds ratio of 2.8. Prospective hormonal monitoring during the early weeks of gestation may be useful in the prediction of early pregnancy loss and should help to avoid the emergency presentation of some of the complications of early pregnancy, in particular ectopic pregnancy. The limitations imposed by multiple pregnancies and uncertain gestation due to menstrual data may restrict the use of this strategy to specialist fertility centres.

New directions in the prevention of adhesion in laparoscopic surgery.

The aim of this review is to appraise critically the literature over the past year with respect to new developments in adhesion prevention strategies. The majority of the work continues to be focused on animal models, and interest continues into the usage of heterologous barriers, which are increasingly derived from or related to hyaluronic acid. The recent trend has been to develop barriers that are not only effective but also technically easy to use for the laparoscopic surgeon--hence the development of barrier gels. It is only through the development of these user-friendly barriers that many laparoscopic surgeons will be willing to incorporate these important preventative measures into their busy daily practice. Routine usage of adhesion prevention measures will ultimately reduce patient morbidity and mortality and relieve the burden on health service provision.

Chromosome abnormalities detected in chorionic villus biopsies of failing pregnancies in a subfertile population.

OBJECTIVE: To determine the range and prevalence of chromosomal abnormalities occurring in failing pregnancies in subfertile women. DESIGN: Prospective biochemical and ultrasound monitoring of all pregnancies conceived between 1988 and 1990 in a subfertile population. SETTING: A single-centre specialist fertility clinic in Perth, Western Australia. SUBJECTS: Tissue from 50 early pregnancy losses was successfully cultured for chromosomal analysis from 46 pregnancies comprising 29 anembryonic pregnancies, 9 miscarriages and 8 ectopic pregnancies. MAIN OUTCOME MEASURES: Impending pregnancy loss was identified at an early stage. Chromosomal analysis was performed on chorionic villi obtained before the diagnosis became clinically evident. RESULTS: Significant chromosomal abnormalities were identified in 54% (14/26) of early pregnancy losses where gamete manipulation was involved and 45% (9/20) of those following spontaneous conception. The most common abnormalities were trisomies (12 pregnancies, mainly trisomy 16), triploidies (3 pregnancies) and monosomy X (3 pregnancies). An excess of female fetuses was noted with only 24% of conceptuses (11/46) bearing a Y chromosome. CONCLUSIONS: The data indicate a similar rate of chromosomal abnormalities underlying pregnancy losses at earlier stages of pregnancy and after infertility treatments as that reported from the general population. Gamete manipulation does not appear to confer a higher rate of chromosomal abnormalities in ensuing pregnancies.

Evaluation of the performance of hysterosalpingo contrast sonography in 500 consecutive, unselected, infertile women.

The performance of hysterosalpingo contrast sonography (Hy Co Sy) as a first-line, outpatient investigation of tubal patency was examined in 500 consecutive, infertile women, at one centre. Hy Co Sy was completed in 463 (92.6%) cases, using a galactose microbubble contrast agent (Echovist-200) and transvaginal sonography. Initial plain scanning identified adnexal pathology in 198 women (39.6%). Examination with Echovist was attempted for 905 tubes and only 67 (7.4%) were not assessable; after the first 100 women this decreased to 35 tubes (4.8%). A sonographic appearance compatible with blocked tubes was found on 118 (14.1%) occasions but it was also possible to identify variations in the appearance/filling/spilling patterns of individual tubes which increased the number assessed as abnormal to 193 (23.0%). Comparison with laparoscopy and dye chromopertubation findings from the past three years was possible for 185 (37%) women, representing 282 tubes, which gave Hy Co Sy an overall concordance rate of 85.8%, sensitivity of 90.4%, specificity of 70.3%, positive predictive value of 91.2% and negative predictive value of 68.2%. Some 51.0% of women described only mild discomfort and there were no significant postprocedure complications. Hy Co Sy appears to be an acceptable first-line screen and may select out women in whom more invasive investigations are likely to reveal pathology.

Is luteal function maintained by factors other than chorionic gonadotrophin in early pregnancy?

Women with ectopic pregnancy (n = 14) and early embryonic arrest ('blighted ovum') (n = 9) were studied 16 days after conception, at a time when they were asymptomatic and serum concentrations of beta-human chorionic gonadotrophin (HCG) were in the normal range and increasing at an apparently normal rate. Serum progesterone and oestradiol concentrations were compared with those from normal women matched for gestational age and serum beta-HCG concentration whose singleton intra-uterine pregnancies proceeded normally beyond 20 weeks. Mean serum progesterone concentrations were significantly lower in the women with ectopic pregnancies than in matched controls (P < 0.002); however, there was no difference in the serum progesterone concentrations between women with blighted ova and matched controls. Statistically significant differences were not seen in serum oestradiol concentrations between either group and matched controls. Similarly there was no difference in serum progesterone or oestradiol concentrations in 20 women who conceived ectopic pregnancies and 20 women conceiving blighted ovum pregnancies and their matched intra-uterine controls when conception followed ovarian stimulation. The low serum progesterone concentrations seen in ectopic pregnancy suggest that there is a specific and selective deficiency in progesterone synthesis, which implies that factors other than HCG may influence luteal function.

Attitudes towards routine human immunodeficiency virus (HIV) screening and fertility treatment in HIV positive patients--a UK survey.

Of 70 fertility units licensed by the Human Fertilisation and Embryology Authority in the UK, 58 responded to a questionnaire regarding attitudes towards human immunodeficiency virus (HIV) screening and fertility treatment in HIV positive patients in November 1995. Of these 58 centres, 23 only performed routine screening for HIV for both partners, 24 for hepatitis B and eight for hepatitis C. In the event of a positive result in the male, fertility treatment would be offered in the form of donor insemination (n = 21), intrauterine insemination (IUI) after sperm washing (n = 21), and in-vitro fertilization (IVF) (n = 1). If the woman was HIV positive, two centres would offer IUI and three centres IVF. Nine centres had already provided treatment for couples in whom the male partner was HIV positive and two centres to HIV positive women.

Perceptions of the quality of life for the adolescent with a chronic illness by teachers, parents and health professionals: a Delphi study.

AIMS: The perceptions that teachers, parents and health professionals have on the relative importance of different aspects of quality of life (QOL) for the adolescent with a chronic illness were explored using a three-round Delphi study. METHODS: The first round questionnaire identified the level of importance each panel attached to 16 aspects relating to QOL. Panellists were also encouraged to provide additional comments on why they felt a particular item was important. In round two, panellists were asked to prioritize the items in order of importance, whereas round three attempted to achieve consensus among each of the three panels. RESULTS: Differences between and within panels in the prioritization of items in round one and round two were evident. However, consensus was achieved in round three, except for the prioritization of very important items by the panel of teachers. Items identified by all three panels as extremely important included the adolescent's attitude, family relationships and friendships with the same age group. Themes to emerge from the qualitative responses to the open-ended questions included the perception of the chronically ill adolescent 'not wanting to be different' and the importance of a 'positive attitude'. The majority of participants also perceived adolescents with a chronic illness as having worse QOL than their healthy counterparts. CONCLUSIONS: By increasing the awareness among the different groups of the impact of chronic illness on various aspects of adolescent QOL, the overall care and support of those adolescents could be improved. Further studies should also be undertaken to explore the views of the chronically ill adolescents themselves.

Routine use of saline hysterosonography in 500 consecutive, unselected, infertile women.

Saline hysterosonography was attempted as a routine, first-line screening test of uterine structure in 500 consecutive, unselected, infertile women. The procedure was completed in 96.8% (484/500) women and the observations were interpretable in 483 of these women. Intrauterine pathology was suspected in 67/499 (13.4%) women on plain ultrasound scan and 58/484 (12%) women with saline hysterosonography. Ultrasound alone had a superior specificity (96.3%) to sensitivity (81.8%) and better negative (97.6%) than positive (73.8%) predictive value for the detection of any intrauterine abnormality, using saline hysterosonography as the reference procedure. Suspected pathology at saline hysterosonography led to hysteroscopy in 20 women, after a median of 5.7 months (range, 1-14). The overall concordance rate between the two procedures was 65% with lesions suspicious of intrauterine polyps not present at subsequent hysteroscopy on six occasions. Criteria were established to help identify women with potentially self-limiting lesions, in whom a re-scan should be considered before resorting to hysteroscopy. The procedure was well tolerated with no significant complications. Saline hysterosonography appeared to be an acceptable first-line screening procedure for uterine structure which enhanced the predictive power of ultrasound alone for uterine anomalies and provided additional information which was potentially of value when planning operative hysteroscopy.

Value of measuring serum FSH in addition to serum estradiol in a coasting programme to prevent severe OHSS.

BACKGROUND: Withholding gonadotrophins (coasting) can reduce the risk of severe ovarian hyperstimulation syndrome (OHSS) in patients having assisted reproduction therapy. This requires daily serum estradiol (E(2)) measurements, which occasionally have been seen to decline suddenly and sharply. METHODS: To increase the sensitivity of the coasting programme we measured serum FSH in parallel with E(2) in patients at risk of developing OHSS. RESULTS: Out of a total of 1240 cycles, 106 were coasted and in 89 both serum E(2) and FSH were measured at least twice during the coasting period. One case of late severe OHSS was encountered in the study group. The serum FSH declined by a rate of 24.3 +/- 4.5% per day. Serum E(2) level reached a 'safe level' of <10,000 pmol/l when the serum FSH declined to 5 IU/l or less. CONCLUSION: The results from this study show that measuring serum E(2) and FSH can assist in predicting the point at which serum E(2) has declined to a level safe enough to administer the trigger HCG.

Excessive follicular response to controlled ovarian stimulation in a woman with menopausal FSH levels: case report.

A suspected poor responder to controlled ovarian stimulation (COS), with menopausal levels of follicular phase serum FSH, required coasting due to an excessive ovarian response. A 27 year old woman was referred to our Fertility Centre for ovum donation following repeated elevated, early follicular phase FSH levels (34.3, 27.1, 20.3 IU/l). Further investigations revealed the presence of antiovarian antibodies and a trial of COS, with the additional use of prednisolone, was proposed in view of her regular 28 day cycle. As 23 follicles were noted and an oestradiol level of 10,461 pmol/l following 7 days of stimulation with 450 IU of recombinant FSH per day, gonadotrophins were withheld for 9 days. Ten oocytes were retrieved and two grade I embryos were transferred. Pregnancy did not occur and she developed mild ovarian hyperstimulation syndrome. During a second cycle, multiple follicular development was again observed with an oestradiol level >13,200 pmol/l, despite a lower dose of gonadotrophin, and coasting was required for 4 days. Nineteen oocytes were collected, of which nine fertilized and cleaved. Two grade I embryos were replaced, leading to a singleton pregnancy. This patient subsequently had a vaginal delivery of a normal male baby at term. Young women with regular menstrual cycles and grossly elevated FSH levels may benefit from further investigation of autoantibodies and their ovarian response to exogenous gonadotrophins.

The impact of adhesions on hospital readmissions over ten years after 8849 open gynaecological operations: an assessment from the Surgical and Clinical Adhesions Research Study.

OBJECTIVE: To investigate the epidemiology of, and the clinical burden related to, adhesions following gynaecological surgery. POPULATION: The Scottish National Health Service Medical Record Linkage Database was used to define a cohort of 8849 women undergoing open gynaecological surgery in 1986. METHODS: All readmissions for potential adhesion related disease in the subsequent 10 years were reviewed. MAIN OUTCOME MEASURES: Readmissions and the degree of adhesion involvement gave an indication of clinical burden and workload. The rate of readmission following the initial surgery determined the relative risk of disease related to adhesions. RESULTS: Two hundred and forty-five (4.5%) of 5433 readmissions following open gynaecological surgery were directly related to adhesions. 34.5% of patients were readmitted, on average 1.9 times, for a problem potentially related to adhesions or for further intra-abdominal surgery that could be complicated by adhesions. Readmissions related to adhesions continued throughout the 10 year period of the study. The overall rate of readmission was 64.0/100 initial operations. For readmissions directly related to adhesions, the rate was 2.9/100 initial operations. Operations on the ovary had the highest rate directly related to adhesions (7.5/100 initial operations), with an overall rate of readmission of 106.4/100 initial operations. CONCLUSIONS: Despite the conservative approach taken in this study, the clinical burden, workload and relative risk of readmissions related to adhesions following open gynaecological surgery was considerable. Post-operative adhesions have important consequences for patients, surgeons and the healthcare system. These results emphasise the need for more effective strategies to prevent adhesions.