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Official panel discussions
EUR.OPEAN JOURN AL OF
OBSTETRICS & GYNECOLOGY AN D REPRODUCTIVE BIOLOGY
ELSEVIER
European Journal of Obstetrics & Gynecology and Reproductive Biology 86 (1999) S3-S8
www.elsevier.com/locate/ejogrb
Official Panel Discussions
Panel Discussion 1 - Clinical implications of molecular screening in gynaecological cancer 1. Genetic mutations: pronostic significance Fernando J. Regateiro, Portugal TEXT NOT AVAILABLE.
2. Genetic mutations: Preventive and therapeutic implications MW. Beckmann, B. Kuschel and H.G. Bender, Department Obstetrics & Gynecology, Heinrich-Heine-Universitdt, Dusseldorf, Germany In the field of gynecology only some hereditary cancer susceptibility syndroms are of importance including those syndromes with genetic alterations of TP53, ATM, PTEN or MSH2, MLH1, PMSI, PMS2, MSH3 and MSH6. Breast, ovarian and endometrial cancers are the most abundant tumour types. Germline mutations of the cancer susceptibility genes BRCAI and BRCA2 seem to be the major part of the hereditary breast/ovarian cancer syndrome (HBOC). Genetic counselling and identification of high-risk families may be essential (I) to provide the best method for genetic testing, (2) to offer the opportunity to participate at specific early cancer detection programs [breast: breast (self) palpation, ultrasound (BUS), mammography (MG), magnetic resonance tomography (MRT); ovary; vaginal exploration (VE) and ultrasound (VUS)], (3) to inform about prophylactic medication [oral contraceptives (OC), chemoprevention (tamoxifen, raloxifen, aromatase inhibitors) or surgery (bilateral prophylactic mastectomy or oophorectomy) and (4) to provide individualized psychological support. To fulfill these widespread demands an interdisciplinary counselling approach (gynecological oncology, human genetics, molecular biology, psychotherapy) in the setting of a cancer genetic clinics seems the most appropriate approach. Therewith participation at predictive genetic testing or the use of preventive or therapeutic options may be discussed extensively with the consultees. Especially, preventive and therapeutic options are emotionally disturbing for the consultees, also in case of previous cancer disease. For breast cancer chemoprevention for high risk women does not seem to be as effective as expected. OC however reduce the risk for ovarian cancer. For prophylactic operations various points have to be considered including: (I) individual risk assessment and gain in life expectancy, (2) value of screening and early detection methods or medical prevention, (4) disease characteristics and prognosis, and (5) anxiety and quality of life. Decision for these options have to be individualized and the psychological support during the period of decision and follow up have to be offered. (Participating Center of Multicenter Project: 'German consortium of familial breast and ovarian cancer' Deutsche Krebshilfe, Germany).
3. Genetic screening: practical implications Stefano Greggi, Italy Cancer genetic counseling for subjects at hereditary risk for cancer is a multistep process through which both genetic and clinical information is conveyed to an individual. Two main components can be identified; risk assessment (empiric/genetic) and counseling on lifestyle, medical and 0301-2115/99/$ - see front matter PH: S0301-2115(99)OOI77-3
surgical options to decrease the risk. The recent introduction of predictive genetic testing into the clinical setting, requires additional efforts to avoid the potential adverse impact of cancer genetic information. Therefore, educational as well as psychological pre and post-test session have become integral parts of the counselling process, requiring a substantial re-modelling of the conventional counselling approach. Clinical implications of genetic testing are many and involved options for surveillance, medical and surgical prevention, all affected by considerable uncertainties. It is too early for an adequate evaluation of the clinical impact of genetic testing. Information data will be available in the next 5-10 years, if the widespread commercial availability of genetic testing will not compromise scientifically rigorous clinical trials.
Panel Discussion 2 - Antenatal care-doing less to achieve more 1. Premature markers. A reality? F. Goffinet, Matemite Port-Royal, Universite Rene Descartes, Paris V, France Classical markers available: Since thirty years many markers have been used to identify high risk patients for preterm delivery (PD). The main criteria are socio-economic factors, past history and symptoms observed during pregnancy (hemmorraghe, uterine contractions, cervical modifications). Scores have been designed to synthetize these informations. Some countries developed prenatal care for prevention of prematurity for the overall population and not only for some women well informed and using medical care (women at lower risk than others). Prematurity's rate is lower in these countries than those without developed prenatal care; however, prematurity and particularly extreme prematurity increased in the past few years in all countries. Many factors can explain this increase but we will not develop all of them. One is that identification of high risk women is not in clinical practice as good as reported in studies. A second point is that interventions after screening doesn't seem effective. Objectives of new markers: Recently many new markers have been evaluated to improve screening (transvaginal ultrasound cervical measurement, fibronectin, bacterial vaginosis, salivary estriol, etc.). It is not sure that the high predictive value reported in these studies would be the same in clinical practice. To recommend systematic use of these new markers in addition to actual markers, several conditions are required. The new test must be simple to perform, have a good reproductibility and not too expensive because of its systematic use. Moreover, its predictive value must be higher than current markers and an effective management must be available after screening. Treatment after screening?: Two treatments could be offered to women at high risk of PD. The first one is a symptomatic management when occuring preterm labor. Almost all cases of spontaneous PD are preceded by preterm labor. Therefore, whatever causes of preterm labor, we will need always a symptomatic intervention which can be beneficial. Controlled randomised trials on home uterine activity monitoring and education showed an increase of early diagnostic of preterm labor and a reduction of PD in a high risk population. Even this symptomatic management (education of women and contact with midwives, bedrest,
© 1999 Elsevier Science Ireland Ltd. All rights reserved.
Official panel discussions / European Journal of Obstetrics & Gynecology and Reproductive Biology 86 (1999) S3-S8
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tocolysis) doesn't decrease prematurity rate, it can decrease neonatal consequences of extreme prematurity. Indeed, tocolysis entails a mean prolongation of gestation of two days with the possibility to give corticoides and organize an in utero tranfer to a level III center. The second treatment is etiologic and could be very effective in preventive and in curative treatment. This management would be focused on populations representing something of a small proportion of the overall prematurity, for instance cerclage of the cervix in case of cervical incompetence or antiobiotics if subclinical infection is diagnosed. Therefore, an etiologic management will never be effective for the entire population. However, inside these particular etiologic groups, it is probably the most effective method. Conclusion: The objective of the new markers is double. We need etiologic markers and symptomatic markers to propose effective management for the entire population. Current markers are not etiological and their predictive value for PD are lower in practice than in experimental studies. Maybe improvement in clinical practice is possible with a better organization of prenatal care. New markers cannot be used in practice before the evaluation of their impact on prematurity. Otherwise physicians will multiply markers, in association or not, without benefice for women. Improvement must be directed firstly to an application more effective of existing screening and prenatal care, secondly, to find interventions more efficacious after screening and maybe at last to the use of new markers, etiologies and symptomatics.
2. Fetal movements and fetus behaviour as tests of fetal well being S. Alexander
1,
M. Delcroix
2,
F. Puech
3, I
School of Public Health,
The incidence of GDM varies with environmental (nutrition) and genetic (ethnicity) conditions. Pregnancies affected by GDM have both short- and long-term effects on the mother and the developing fetus. Pregnancy induced hypertension, premature labor and operative delivery are more prevalent in GDM mothers; premature birth, increased perinatal mortality, macrosomia, birth traumata and neonatal hypoglycemia threaten their offspring. Long-term studies show that GDM is a predictor for the occurence of type 2 diabetes with all its sequelae in affected women. Furthermore, children from pregnancies complicated by GDM themselves face severely increased risks of obesity, impaired glucose tolerance and development of type 2 diabetes mellitus later in life. The statement 'Diabetes begets Diabetes' shows the social dimension of a medical problem at a time, when the prevalence of type 2 diabetes is increasing dramatically in industrialized countries. Therefore, early detection and treatment of GDM may not only be beneficial in the affected pregnancy but may very well yield longterm benefits for women, children and a population's health status.
Panel Discussion 3 . Hormonal Replacement Therapy in Europe 1, The brain as a target for HRT A.R. Genazzani 1, F. Bernardi 1, M. Stomati 1, P. Monteleone 1, S. Luisi 1, E. Casarosa 1, M. Luisi 2, I Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, 2 CNR, Endocrine Research Unit, Pisa, Italy
3, Gestational diabetes mellitus· A social problem?
The brain is an important target tissue for sex steroid hormones. Estrogens, progestins and androgens are able to induce several effects in the central nervous system (CNS), through genomic effects and nongenomic mechanisms. During the climacteric period, estrogen deficiency at the hypothalamic level, gives rise to vasomotor symptoms, as well as to eating behaviour disorders and altered blood pressure control. Noradrenergic, dopaminergic and opioidergic tones appear to be involved in the control of hypothalamic centers. On the other hand, at the limbic level, changes in serotoninergic, noradrenergic and opioidergic tones contribute to the modifications in mood, behaviour and nociception. The positive effects that HRT determine on vasomotor symptoms and mood appear to be related to the activity on various neurotransmitters and neuropeptides. Clinical studies in climacteric women frequently report a decrease in cognitive efficiency, reverted by estrogen administration which improves memory and reaction time. Many biologicial mechanisms support the evidence that estrogens protect from Alzheimer's disease by influencing the cholinergic tone, increasing cerebral blood flow, modulating growth proteins associated with axonal elongation and blunting the neurotoxic effects of j3-amyloid. Concerning progestagens a negative modification of mood has been described in clinical trials using different combination of estrogen and progestin compounds. These actions are probably due to the active metabolites of progesterone, such as allopregnanolone, 17-OH pregnanolone and 17-0H progesterone by enhancing MAO activity and the GABA-induced decrease in brain excitability. Few studies have focused their attention on 85 androgen replacement therapy and in particular on the symptoms directly related to androgen deficiency, such as sexual disorders, loss of well-being and energy, mood disorders, metabolic and bone mass effects. DHEA and DHEAS are considered neurosteroids because they are also produced in the CNS. Neurosteroids modulate cerebral function, indicating that the modifications in mood and cognitive performances occurring in postmenopausal women could be related to a modification in neurosteroidogenesis. The administration of DHEA, a GABA-A antagonist, improves physical and psychological well-being and cognitive performances in aged subjects, probably by antagonizing the effects of cortisol leading to a progressive hippocampal damage. These findings open new perspectives for the study of the effects of sex steroids on CNS and for a possible use of alternative and/or auxiliary HRT.
U. Lang and W. Kiinzel, Department of Obstetrics and Gynecology, University of Giessen, Germany
2. Continuous combined therapy
Gestational diabetes mellitus (GDM) is defined as 'carbohydrate intolerance of variable severity with onset or first recognition during pregnancy'.
Continuous combined therapy (CCT) has been pioneered in Scandinavia
Universite Libre de Bruxelles, 2 Maternite Saint Philibert, Universite Catholique de Lille, 3 Hupital Jeanne de Flandre, Universite de Lille, Belgium Fetal movements: It has long been known that a healthy fetus should move actively, and that the mother should perceive these movements. It was therefore suggested that by asking pregnant women to formally count fetal movements it might be possible to decrease the toll of unexplained fetal death. From 1986 to 1987, in 5 countries, 68,000 women were randomly allocated within thirty-three pairs of clusters either to a policy of routine counting or to standard care, which might involve selective use of formal counting or informal noting of movements. Antepartum death rates for normally formed singletons were similar in the two groups, regardless of cause or prior risk status. This disappointing result prompted further research. It was then suggested that the counting schedule of fixed time versus fixed number of movements might be important and from 1989 to 1990, a multi-center French study assessed feasibility of counting. This study and a review of other relevant studies show that mothers consider that counting is time consuming and demanding. Furthermore, it is very difficult to establish an optimal counting schedule. The data, both from the French study and from compilation of the literature indicate, beyond reasonable doubt that the duration of counting has a direct influence on the number of kicks perceived. The shorter the counting time, the greater the number of kicks perceived per hour. Despite the exceptionally high order of magnitude of this variation is has not yet been reported as such. Biophysical profile (BPP): On the other hand, the use of Manning score may well be one of the most performing tests to decide, in presence of chronic fetal distress, whether to let the pregnancy continue or to intervene. Unfortunately, despite the excellent reports from the literature, there is not as yet a sufficiently large randomised trial of BPP in impaired fetal growth. This may well be because BPP requires a skilled ultrasound scanner and lasts on average 20 minutes. In most countries this is a double deterrent, especially where fee for service is the usual mode of retribution and BPP cannot be billed differently from a standard USS.
D. Sturdee, Department of Women's Health, Solihull Hospital, UK
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and Europe, and is becoming increasingly popular due to the improved long term compliance. The main purpose and benefit of the continuous progestogen is the prevention of period-type bleeds, which can be achieved in at least 75% of postmenopausal women, and higher proportions of older women. Persistent or new bleeding in women established on CCT is often associated with the finding of an endometrial polyp or submucous fibroid. An atrophic endometrium is produced and maintained in about 90% of women, and hyperplasia without atypia has rarely been reported. There have been no reports of endometrial carcinoma developing in women from a normal endometrium while taking CCT. Furthermore, a large UK study reported that when complex endometrial hyperplasia was found in women taking standard sequential oestrogen/progestogen regimens, this was converted to normal by CCT. The continuous progestogen does not prevent the beneficial effects of oestrogen on the lipid profile. On-going randomised placebo-controlled studies of secondary prevention of coronary heart disease using CCT regimens, will determine the extent of benefits for cardiovascular disease. New low dose combinations with Img oestradiol or equivalent seem to be as effective in symptom control and prevention of osteoporosis, and arc associated with fewer side effects and bleeding. They will be particularly suitable for older postmenopausal women.
Hormone replacement therapy (HRT), given as unopposed oestrogens as well as combined oestrogen-progestogen replacement, has been associated with a 40-60% reduced risk of developing cardiovascular disease in postmenopausal women. Also experimental studies in animals and humans have demonstrated the anti-atherogenic effects of HRT. The cardiovascular protection of HRT probably results from changes in a variety of risk markers, of which the number is still growing. HRT has been reported to beneficially influence e.g. the lipids and lipoproteins, depending however on the formulation's dosages, the route and duration of administration, and the type of progestogen. The contribution of modulating conventional lipids to cardiovascular protection has been estimated to be about 25%. Other potential mechanism related to HRT induced risk reductiuon are effects on: I) lipoprotein(a); 2) LDL-oxidation; 3) coagulation and fibrinolysis; 4) glucose metabolism; 5) endothelial factors; 6) homocysteine metabolism; 7) impedance to (peripheral) blood flow, and 8) cardiac function. Many, but not all, effects reported so far of HRT on these new markers are beneficial from the cardiovascular point of view. This presentation will discuss some of these mechanisms in more detail.
3. Women's health in Lund area (WHILA) study
Panel Discussion 4 - Can we minimize surgical techniques in urogynaecology
G. Samsioe, J. Lidfelt, L. Holmdahl, C. Nerbrand, B. Schersten, L. Lindholm and C.D. Agardh, Lund Universiy Hospital, Lund, Sweden The WHILA cohort aims at recruiting all women (n= 10.890) living in Lund area and born between 1935 and 1945. A questionnaire comprising 103 questions is mailed together with an invitation to undergo a healthscreening programme. At the Health Care Centre all women are personally interviewed by a specially trained nurse midwife and the basic questionnaire discussed. Interview results in changes in about 19% of the questionnaires. At this interview a second questionnaire is given to some women dependent on the answers to certain questions. A laboratory test is carried out comprising a serum lipid profile, bone mass measurement, blood pressure, waist-hip ratio and body mass index. In addition, extra blood samples are drawn and serum are stored in 5 aliquots in -70 freezes together with I aliquot of white blood cells in order to perform specific analysis of various factors which are optional. Should laboratory values fall outside certain limits, a secondary screening procedure is performed, which among other things comprises duplicate oral glucose tolerance tests with concomitant insulin determinations, thyroid function, ECG, fasted serum lipoprotein profile, HbAlC and microalbuinuria. Out of 7,200 women investigated first, II % were premenopausal (Plvl-group), 55% postmenopausal without HRT (PMT-group) and 34% postmenopausal with HRT (PMT-group). Of the latter 83% were current users. Furthermore, 19% were overweight (BMI>28) and 11% obese (BMI>30). A fasting 2 hour 75 g oral glucose tolerance test (OGTT) was performed in 1.227 women who had a 'positive' primary screening. Of these women (7%) had an impaired glucose tolerance and 1.3% had overt diabetes hitherto undiagnosed. There was a positive statistical assoiation between the random blood glucose and BMI, waist-hip ratio (p<0.02), systolic blood pressure (p
4. Mechanistic aspects of cardiovascular protection by hormone replacement therapy MJ. van der Mooren. Project 'Ageing Women' and Institute for Cardiovascular Research, Department of Obstetrics and Gynaecology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands
1. TVT-procedure Carl Gustav Nilsson, Finland
TEXT NOT AVAILABLE.
2. Traditional procedures E. Petri, Chief Dept. Obstetrics & Gynecology, Schwerin Medical School, Germany Introduction: Over the decades there have been described more than 200 different surgical procedures, modifications and submodifications for the treatment of female urinary incontinence. Gynecologists still tend to the vaginal procedures in their belief of anatomical reconstruction being the major aim of cure of sphincter incompetence. Prospective and controlled randomised studies in recent years have been able to demonstrate superiority of abdominal approaches. Surgical concept: There are two pathophysiological concepts for the approach: I. repositioning of the prximal urethra back into the abdominopelvic pressure transmission zone (e.g. colposuspension or slings); 2. Refixation of torn ligaments to the mid-urethra (TVT). Colposuspension as first described by BURCH and modified by many others has merged to be the gold-standard, giving good long-term results subjectively and objectively in follow-ups up to more than 20 years between 60-80%. We performed more than 1800 modified colposuspensions since 1985 reaching cure rates in a follow-up of up to 12 years in primary cases between 80 to 88%, 71% in recurrencies. In detailed follow-up of subjective data we had to learn that complete satisfaction of the patients in spite of complete continence is reduced by obstructive micturition and particularly in hard working women of pain in the area of fixation ('colposuspension-syndrome'). But, these symptoms should be the same in endoscopic techniques. In hypotonic urethra (lSD) and repeated recurrencies so far we performed a fiscal sling procedure in the technique described by NARIK and PALMRICH. Fairly good success rates were accompanied by an important rate of complications like obstructive voiding up to retention, secondary urgency, hernias and pain. We are changing at the present time to the tension free vaginal tape (TVT). Therapeutical strategy: After exhausting all conservative regimens including estrogen replacement, physiotherapy, cones and electrotherapy and, after urodynamic and morphologic proof of sphincter incompetence the aim of surgical therapy should be reconstruction of clinically relevant and symptomatic pelvic floor defect together with either are-positioning of the bladder neck back into the abdomino-pelvic equilibrium, in the future perhaps waiting for scar tissue fixation by TVT.
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Official panel discussions I European Journal of Obstetrics & Gynecology and Reproductive Biology 86 (1999) S3-S8
3. Laparoscopic procedures
J.M. Lavin, Dept. of Urological Gynaecology, St. Mary's Hospital, Manchester, UK Advances in imaging and instrument design has enabled surgeons to perform standard operations laparoscopically. The aim is to reproduce the results of the standard procedures but with the perceived advantages of minimal access surgery. Laparoscopic colposuspension was first reported in 1991 and since that time there have been many series reported in the literature, however, the patient selection, technique employed and follow up have not been consistent. In the majority of series, there has only been short term subjective follow up data available. Laparoscopic paravaginal repair, vault suspension and posterior vaginal wall support have all been reported. This talk will critically review the published data on laparoscopic procedures for the treatment of urogynaecological disorders.
Results: The cross-sectional study showed that steroid therapy was associated with the thinnest skin measurements (0.83 mm) obtained for all patients screened at the menopause clinic. Similarly, low bone density measurement, lumbar spine (0.81 g/cm)", hip (0.71 g/cmj" were obtained for patients on long term standing therapy. Twelve women had sustained single or multiple fractures. Since the establishment of the bone density unit 38 patients who had been on long term steroid have been followed up after the administration of oral hormone replacement therapy [Prempak C 0.625 mg]. This longitudinal study revealed a constant increase in skin thickness [6% per year] and bone density [left hip 5%, lumbar spine 4%].
3. Preventive care in breast cancer M. Birkhauer, Head, Div. of Gynaecological Endocrinology, UniversitdtsFrauenklinik Bern, Inselspital, Schanzeneckstrasse I, CH-30I2 Berne, Switzerland
Preventive care in breast cancer consisted until now mainly in regular clinical and paraclinical examinations of the breast:
4. Comparative studies of old and new techniques
Paul Hilton, UK TEXT NOT AVAILABLE.
Panel Discussion 5 - Women's Health Care 1. Cardiovascular disease in women and preventive care
G. Samsioe, Dept. of Obstetrics & Gynecology, Lund University Hospital, Lund, Sweden A growing body of evidence suggests that oestrogen replacement therapy is beneficial for women's risk of osteoporotic fractures and heart disease. A woman at 50 carries about a 50% risk of coronary heart disease and a 30% risk of dying from it. Oestrogen monotherapy greatly reduces the risk of several cardivascular manifestations, such as myocardial infarctions and stroke by approximately 50% in primary preventative trials. Even if confounding and bias are present in observational studies a randomised clinical trial may alter the exact relative risk but it is not likely to afflict the concept of cardioprotection by ERT. Angiographic studies reveal that women with the most severe stenosis are those who have the most to gain from oestrogen therapy. It can be inferred from these studies that the two major mechanisms for cardioprotection are direct effects on vessel wall leading to a vasodilatation and reduced arteriosclerosis formation. Reasons for atherosclerosis are multifold, but serum lipid and lipoprotein metabolism is considered to play a pivotal role in this respect. Oestrogens can be shown to increase HDL, lower total and LDL cholesterol and lipoprotein (a) as well as to be an antioxidant. The addition of a progestogen lowers HDL and triglycerides and further lowers total and LDL cholesterol and lipoprotein (a) and has no impact on antioxidant effects. Albeit limited, observational studies on combined hormone therapy agree that there is no attenuation by the addition of a progestogen to oestrogen regardless of the nature of the progestogen. 2. Primary and preventive osteoporosis care
M. Brincat, Y. Muscat Baron, R. Galea. Departent of Obstetrics and Gynaecology, University of Malta, Medical School of Malta, Msida, Malta Introduction: Long term steroid therapy is complicated by osteoporosis and generalised thinning of the skin. These two complications of long term steroid therapy are routinely assessed at the menopause clinic of St. Luke's Hospital. Patients and methods: A cross-sectional study was performed on 164 postmenopausal women who had been on long term corticosteroid therapy. A longitudinal study on 38 postmenopausal women on long term steroid therapy was performed. Each women had the skin thickness measured by high resolution ultrasound (22 MHz) and the bone density measured by a DEXA-Norland 386.
• annual clinical examination of the breast • mammography and/or sonography every two years in the normal population, every year in high risk patients Recently, the preventive administration of antihormones or SERM's (Selective Estrogen Receptor Modulators) has been proposed in high risk patients, based on preliminary data obtained with Tamoxifene and Raloxifene. A first study using Tamoxifene resulted in a lower incidence of breast cancer in the Tamoxifene group, suggesting a reventive effect of SRM's. However, these data have not been confirmed by two other studies. The preliminary data obtained in the Raloxifene trials are encouraging. Although they are based on a relatively low number of cancers, a preventive effect on breast cancer is likely. However, there are no data on mortality in women having received a preventive administration of SERM's. SERM's could select receptor-neg. tumours and therefore more aggressive cancers. Before general recommendations can be made, the risks and the benefits of a preventive administration of SERM's have to be thoroughly evaluated by large additional prospective trials
4. Estrogens may prevent CNS diseases in women
Manuel Neves-e-Castro, Av. Antonio de Aguiar, 24, 2° D, 1050-016 Lisbon, Portugal It is now well established that the brain is a target for sex steroidal hormones trough genomic and non-genomic mechanisms of action. Experimental studies indicate that estrogen deprivation causes a decrease in brain neuro transmitters and that estrogens can reverse such changes. Post-menopausal women often suffer from brain disfunctions that may cause mood changes, decreases in cognition and memory, etc. Estrogen replacement may improve such disorders in many women suggesting that these hormones have an effect in brain organization. Furthermore, estrogens maintain brain circulation and have pronounced effects in lipoprotein metabolism, thus contributing to a better brain function. There is growing evidence that estrogens given to postmenopausal women may decrease and ameliorate their symptomatology. Therefore, hormone replacement therapy given to postmenopausal women has positive effects on CNS derived symptoms, in the short term, and may have preventive actions in the long term.
Panel Discussion 6 - Long term consequences of infertility treatment for mother and child 1. Complications of induction ovulation
J. Schenker, Israel TEXT NOT AVAILABLE.
Official pa nel discuss ions I European Jou rnal of Obstetrics & Gynecolo gy and Reproductive Biology 86 ( 1999) 53 -58
2. Genetic risks of IVF/ICSI Madalena Barata, Campo Grande 30. l 'T), Po rtugal Mushin in 1985 published on Clin. Obstet. Gynaecol., a ration ale for the study of IVF children. The focus of this paper was to determine whether or not a significant risk involving these children. Hurst from Syndey in 1997 presented figures for 1979-1995, showing 2.5% of infants and foetuses with major congeni tal malformations. This rate in the normal population is similar. Concerning long term follow-up of a large series of children born after ICSI, at this time there is none. However, genetic defects associa ted with male fertility pro blems can be transmitted to offspring. E. Legins group from the centre for Human Genetic s, Gasthuisberg, Leuven started a prospective study of 388 males with fertili ty problems. Chromosomal abnormalities, mutatio ns in the cystic fibrosis gene, and microdeletions on the Y chromosome are in analysis .
3. ART and gynecological malignancies
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4. Health of the children conceived with IVF/ICSI F. Olivennes, France The first IVF children are 20 years old. Since then, major progress has been made in various aspects of IVF and the number of children conceived with the help of IVF is incre asing. Very few reports have been published on the long-term follow- up of IVF children. Most of these studies are presenting reassuring data , but the methodology of nearly all of them do not allow to conclude that IVF has no detrimental effect on the grow th and on the motor and psycho logical development of the children conceived with this technique. The differe nces existing betwee n fertile and infertile couples make the pediat ric follow-up studies very difficult to organise , especially for the choice of a control group. The major difficulties are the number of children to be included, the type and exte nt of evaluation, the length of the follow-up, the risk of high rate lost for follow-up. There is also a clear ethical problem to singularise IVF children by enrolling them in specific medical and psychological studies. However, the evaluation of the assisted reproductive technologies is mandatory, and the well-being of the children has to be evaluated especially with the new techniqu es used with gametes and embryos.
P.N. Barri, M. Izquierdo, B. Corole u, Service of Reproductive Medicine, Depa rtment of Obstetrics and Gynaecology , Institut Universitari Dexeus, Barcelona, Spain The aetiology of many gynaecological cancers is, even today. poorly understood. It is known that women who have no had children run a higher risk of cance r of the breast, of the ovary and of the endometrium, a close relationship having been established betwee n the age of the first birth and the risk of cance r of the breast. Although the greater risk of gynaecological cancer in childless women appears to be due to the fact of their involunary infertility and the logical absence of known protection factors such as multiparity and lactati on, it is incumbent upon us to deepe n our knowledge of the risks additional to those to which involuntarily infertile patient may be subjected. Present-day Assisted Reproduction technciques, with their usual protocols of stimulation of follicular develop ment by means of drugs such as clomiphene citrate and the gonadotrophins, have been suggested as possible additional riks factors in infertile patients with respect to cancer of the breast, ovary and endometrium. We have evalu ated the incide nce of gynaecological cancer among the first 900 patients who underwent ovarian stimulation with a view to IVF in our Institute and who were followed up for more than 10 years (7,917 years of follow-up). Among these patients we found 2 cases of breast cancer and I case of ovarian cancer. At the same time we analysed the data of a historical group of 5 patients from our Service of Reprodu ctive Medicine and not included above who presented a gynaec ological cancer in their follow-u p. The first evalua tion which we must make is epidemio logica l, bearing in mind the expected incidence and that encountered in our sample with regard to the protection and risk factors presented by the patients included in the follow-up . We took as a standard or reference population the population of the province of Tarrago na and their cance r register during the period 1984-1 987. From these data we obtained an estimat ion of the expected cases taking as a starti ng point the specific levels of incidence by age and sex from this register. According to our data in our study population 2.3 cases of breast cancer, 1.08 cases of ovarian cancer and 2.1 cases of endometrial cancer should have been expected. The observation of 2 breast eancers and one ovarian cancer does not supply us with standard ised Morbidity Indices (S.M.!.) which are lower than unitr, which leads us to think that we have not observed more cases than would have been expected. Great care must be taken in analysing all these data since some of the diffe rences observed between the groups may be due to what are still very prelimi nary results which may be affected by some statistical anomaly. For this reason this study remains open to include more patients and extend their follow -up. Continued study of a large number of cases may change some of the tendencies or confirm others. We must not forget the risk factors which these patients have by virtue of being inferti le. In our study we have not been able to discern differences with respect to the post-treatment pregna ncy of the two groups We shall probably reach the conviction that much wider multi-centre studies will be needed in order to draw definitive conclus ions.
EBCOG Training Session - Training in obstetrics and gynaecology 1. EBCOG's recommendations on tra ining Jacques Lansac, France TEXT NOT AVAILABLE.
2. Quality control J.W. Wladimiroff, Department of Obstet rics & Gynaecology. University Hosp ital Rotterdam-Dijkzigt, Rotterdam, The Netherlands Since EBCOG came into being in September 1996, the organisation has made considerable progress both in its working parties and its relations hip with other organisations, such as EAGO . One of the Working Parties is the Hospital Visiting Committee which aims at ensuring quality contro l of specialist training of its training units in Europe. Up until now, 16 academi c centres have been visited in countries like Norway, Slovenia, Germany, Portugal, France, Spain, The Netherlands and Hungary . The visits, so far, are considered very succe ssful by both the visitors and visited. Emphasis lies on the training system which includes the presence of a struct ured training programme , sufficient training facilities, adequate theoretical training, a tutorial system and continuo us assessment of practical skills and theoretical knowledge. It has become clear that in some countries national labour policies have a direct impact on the quality of traini ng. Thi s implies that EBCOG - through the UEMS should have access to sending the recommendations coming out of the visits to a higher health care level (Ministry of Health) in the host country . Struct ured revisits should take place every five years. Natio nal societies should take over the visiting process after 5- 10 visits to the host country pending on the acquisi tion of sufficient experience in the visiting process and the implementation of a well-organised national visiting system.
3. Training In obstetrics and gynaecology - the trainees opinion Filome na Nunes , President of the European Netwo rk of Trainee s in Obstetrics and Gynaec ology
In 1975 the European Union of Medical Specialists , participated in the definition of the European Medical Directives, that regualte the free movement of doctors and mutual recog nition of medical credentials, throughout the European Communi ty. Training in Obstetrics and Gynaecology in Europe is still quite heterogeneous reflecting the cultural, social and ethical differences .
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Official panel discussions I European Journal of Obstetrics & Gynecology and Reproductive Biology 86 (1999) 83-88
Nevertheless many countries do seem to be approaching a standard, for example the duration of training is now fairly uniform. The definition and recommendations on what is basic and should be common to all countries will help to achieve quality control in training. Quality control in training: training programs, training centres, trainers and trainees. The European Network of Trainees in Obstetrics and Gynaecology (ENTOG) was created in 1996, to establish communication and represent the European trainees. The aims of ENTOG are to promote a better understanding of training in Obstetrics and Gynaecology in Europe thus ensuring comparable and high standards of training.
The position of the European Board and College of Obstetrics and Gynaecology working in co-operation with the National Authorities of each country and the trainees was an important step to allow the establishment of common European Recommendations for training. It is unlikely that complete harmon isation of training in Obstetrics and Gynaecology is possible in Europe. However, it is hoped that if the EBCOG recommendations are implemented by all Europe an countries then a certain quality of training will be assured.
OBSTETRICS & GYNECOLOGY AN D REPRODUCTIVE BIOLOGY
ELSEVIER
European Journal of Obstetrics & Gynecology and Reproductive Biology 86 (1999) S3-S8
www.elsevier.com/locate/ejogrb
Official Panel Discussions
Panel Discussion 1 - Clinical implications of molecular screening in gynaecological cancer 1. Genetic mutations: pronostic significance Fernando J. Regateiro, Portugal TEXT NOT AVAILABLE.
2. Genetic mutations: Preventive and therapeutic implications MW. Beckmann, B. Kuschel and H.G. Bender, Department Obstetrics & Gynecology, Heinrich-Heine-Universitdt, Dusseldorf, Germany In the field of gynecology only some hereditary cancer susceptibility syndroms are of importance including those syndromes with genetic alterations of TP53, ATM, PTEN or MSH2, MLH1, PMSI, PMS2, MSH3 and MSH6. Breast, ovarian and endometrial cancers are the most abundant tumour types. Germline mutations of the cancer susceptibility genes BRCAI and BRCA2 seem to be the major part of the hereditary breast/ovarian cancer syndrome (HBOC). Genetic counselling and identification of high-risk families may be essential (I) to provide the best method for genetic testing, (2) to offer the opportunity to participate at specific early cancer detection programs [breast: breast (self) palpation, ultrasound (BUS), mammography (MG), magnetic resonance tomography (MRT); ovary; vaginal exploration (VE) and ultrasound (VUS)], (3) to inform about prophylactic medication [oral contraceptives (OC), chemoprevention (tamoxifen, raloxifen, aromatase inhibitors) or surgery (bilateral prophylactic mastectomy or oophorectomy) and (4) to provide individualized psychological support. To fulfill these widespread demands an interdisciplinary counselling approach (gynecological oncology, human genetics, molecular biology, psychotherapy) in the setting of a cancer genetic clinics seems the most appropriate approach. Therewith participation at predictive genetic testing or the use of preventive or therapeutic options may be discussed extensively with the consultees. Especially, preventive and therapeutic options are emotionally disturbing for the consultees, also in case of previous cancer disease. For breast cancer chemoprevention for high risk women does not seem to be as effective as expected. OC however reduce the risk for ovarian cancer. For prophylactic operations various points have to be considered including: (I) individual risk assessment and gain in life expectancy, (2) value of screening and early detection methods or medical prevention, (4) disease characteristics and prognosis, and (5) anxiety and quality of life. Decision for these options have to be individualized and the psychological support during the period of decision and follow up have to be offered. (Participating Center of Multicenter Project: 'German consortium of familial breast and ovarian cancer' Deutsche Krebshilfe, Germany).
3. Genetic screening: practical implications Stefano Greggi, Italy Cancer genetic counseling for subjects at hereditary risk for cancer is a multistep process through which both genetic and clinical information is conveyed to an individual. Two main components can be identified; risk assessment (empiric/genetic) and counseling on lifestyle, medical and 0301-2115/99/$ - see front matter PH: S0301-2115(99)OOI77-3
surgical options to decrease the risk. The recent introduction of predictive genetic testing into the clinical setting, requires additional efforts to avoid the potential adverse impact of cancer genetic information. Therefore, educational as well as psychological pre and post-test session have become integral parts of the counselling process, requiring a substantial re-modelling of the conventional counselling approach. Clinical implications of genetic testing are many and involved options for surveillance, medical and surgical prevention, all affected by considerable uncertainties. It is too early for an adequate evaluation of the clinical impact of genetic testing. Information data will be available in the next 5-10 years, if the widespread commercial availability of genetic testing will not compromise scientifically rigorous clinical trials.
Panel Discussion 2 - Antenatal care-doing less to achieve more 1. Premature markers. A reality? F. Goffinet, Matemite Port-Royal, Universite Rene Descartes, Paris V, France Classical markers available: Since thirty years many markers have been used to identify high risk patients for preterm delivery (PD). The main criteria are socio-economic factors, past history and symptoms observed during pregnancy (hemmorraghe, uterine contractions, cervical modifications). Scores have been designed to synthetize these informations. Some countries developed prenatal care for prevention of prematurity for the overall population and not only for some women well informed and using medical care (women at lower risk than others). Prematurity's rate is lower in these countries than those without developed prenatal care; however, prematurity and particularly extreme prematurity increased in the past few years in all countries. Many factors can explain this increase but we will not develop all of them. One is that identification of high risk women is not in clinical practice as good as reported in studies. A second point is that interventions after screening doesn't seem effective. Objectives of new markers: Recently many new markers have been evaluated to improve screening (transvaginal ultrasound cervical measurement, fibronectin, bacterial vaginosis, salivary estriol, etc.). It is not sure that the high predictive value reported in these studies would be the same in clinical practice. To recommend systematic use of these new markers in addition to actual markers, several conditions are required. The new test must be simple to perform, have a good reproductibility and not too expensive because of its systematic use. Moreover, its predictive value must be higher than current markers and an effective management must be available after screening. Treatment after screening?: Two treatments could be offered to women at high risk of PD. The first one is a symptomatic management when occuring preterm labor. Almost all cases of spontaneous PD are preceded by preterm labor. Therefore, whatever causes of preterm labor, we will need always a symptomatic intervention which can be beneficial. Controlled randomised trials on home uterine activity monitoring and education showed an increase of early diagnostic of preterm labor and a reduction of PD in a high risk population. Even this symptomatic management (education of women and contact with midwives, bedrest,
© 1999 Elsevier Science Ireland Ltd. All rights reserved.
Official panel discussions / European Journal of Obstetrics & Gynecology and Reproductive Biology 86 (1999) S3-S8
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tocolysis) doesn't decrease prematurity rate, it can decrease neonatal consequences of extreme prematurity. Indeed, tocolysis entails a mean prolongation of gestation of two days with the possibility to give corticoides and organize an in utero tranfer to a level III center. The second treatment is etiologic and could be very effective in preventive and in curative treatment. This management would be focused on populations representing something of a small proportion of the overall prematurity, for instance cerclage of the cervix in case of cervical incompetence or antiobiotics if subclinical infection is diagnosed. Therefore, an etiologic management will never be effective for the entire population. However, inside these particular etiologic groups, it is probably the most effective method. Conclusion: The objective of the new markers is double. We need etiologic markers and symptomatic markers to propose effective management for the entire population. Current markers are not etiological and their predictive value for PD are lower in practice than in experimental studies. Maybe improvement in clinical practice is possible with a better organization of prenatal care. New markers cannot be used in practice before the evaluation of their impact on prematurity. Otherwise physicians will multiply markers, in association or not, without benefice for women. Improvement must be directed firstly to an application more effective of existing screening and prenatal care, secondly, to find interventions more efficacious after screening and maybe at last to the use of new markers, etiologies and symptomatics.
2. Fetal movements and fetus behaviour as tests of fetal well being S. Alexander
1,
M. Delcroix
2,
F. Puech
3, I
School of Public Health,
The incidence of GDM varies with environmental (nutrition) and genetic (ethnicity) conditions. Pregnancies affected by GDM have both short- and long-term effects on the mother and the developing fetus. Pregnancy induced hypertension, premature labor and operative delivery are more prevalent in GDM mothers; premature birth, increased perinatal mortality, macrosomia, birth traumata and neonatal hypoglycemia threaten their offspring. Long-term studies show that GDM is a predictor for the occurence of type 2 diabetes with all its sequelae in affected women. Furthermore, children from pregnancies complicated by GDM themselves face severely increased risks of obesity, impaired glucose tolerance and development of type 2 diabetes mellitus later in life. The statement 'Diabetes begets Diabetes' shows the social dimension of a medical problem at a time, when the prevalence of type 2 diabetes is increasing dramatically in industrialized countries. Therefore, early detection and treatment of GDM may not only be beneficial in the affected pregnancy but may very well yield longterm benefits for women, children and a population's health status.
Panel Discussion 3 . Hormonal Replacement Therapy in Europe 1, The brain as a target for HRT A.R. Genazzani 1, F. Bernardi 1, M. Stomati 1, P. Monteleone 1, S. Luisi 1, E. Casarosa 1, M. Luisi 2, I Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, 2 CNR, Endocrine Research Unit, Pisa, Italy
3, Gestational diabetes mellitus· A social problem?
The brain is an important target tissue for sex steroid hormones. Estrogens, progestins and androgens are able to induce several effects in the central nervous system (CNS), through genomic effects and nongenomic mechanisms. During the climacteric period, estrogen deficiency at the hypothalamic level, gives rise to vasomotor symptoms, as well as to eating behaviour disorders and altered blood pressure control. Noradrenergic, dopaminergic and opioidergic tones appear to be involved in the control of hypothalamic centers. On the other hand, at the limbic level, changes in serotoninergic, noradrenergic and opioidergic tones contribute to the modifications in mood, behaviour and nociception. The positive effects that HRT determine on vasomotor symptoms and mood appear to be related to the activity on various neurotransmitters and neuropeptides. Clinical studies in climacteric women frequently report a decrease in cognitive efficiency, reverted by estrogen administration which improves memory and reaction time. Many biologicial mechanisms support the evidence that estrogens protect from Alzheimer's disease by influencing the cholinergic tone, increasing cerebral blood flow, modulating growth proteins associated with axonal elongation and blunting the neurotoxic effects of j3-amyloid. Concerning progestagens a negative modification of mood has been described in clinical trials using different combination of estrogen and progestin compounds. These actions are probably due to the active metabolites of progesterone, such as allopregnanolone, 17-OH pregnanolone and 17-0H progesterone by enhancing MAO activity and the GABA-induced decrease in brain excitability. Few studies have focused their attention on 85 androgen replacement therapy and in particular on the symptoms directly related to androgen deficiency, such as sexual disorders, loss of well-being and energy, mood disorders, metabolic and bone mass effects. DHEA and DHEAS are considered neurosteroids because they are also produced in the CNS. Neurosteroids modulate cerebral function, indicating that the modifications in mood and cognitive performances occurring in postmenopausal women could be related to a modification in neurosteroidogenesis. The administration of DHEA, a GABA-A antagonist, improves physical and psychological well-being and cognitive performances in aged subjects, probably by antagonizing the effects of cortisol leading to a progressive hippocampal damage. These findings open new perspectives for the study of the effects of sex steroids on CNS and for a possible use of alternative and/or auxiliary HRT.
U. Lang and W. Kiinzel, Department of Obstetrics and Gynecology, University of Giessen, Germany
2. Continuous combined therapy
Gestational diabetes mellitus (GDM) is defined as 'carbohydrate intolerance of variable severity with onset or first recognition during pregnancy'.
Continuous combined therapy (CCT) has been pioneered in Scandinavia
Universite Libre de Bruxelles, 2 Maternite Saint Philibert, Universite Catholique de Lille, 3 Hupital Jeanne de Flandre, Universite de Lille, Belgium Fetal movements: It has long been known that a healthy fetus should move actively, and that the mother should perceive these movements. It was therefore suggested that by asking pregnant women to formally count fetal movements it might be possible to decrease the toll of unexplained fetal death. From 1986 to 1987, in 5 countries, 68,000 women were randomly allocated within thirty-three pairs of clusters either to a policy of routine counting or to standard care, which might involve selective use of formal counting or informal noting of movements. Antepartum death rates for normally formed singletons were similar in the two groups, regardless of cause or prior risk status. This disappointing result prompted further research. It was then suggested that the counting schedule of fixed time versus fixed number of movements might be important and from 1989 to 1990, a multi-center French study assessed feasibility of counting. This study and a review of other relevant studies show that mothers consider that counting is time consuming and demanding. Furthermore, it is very difficult to establish an optimal counting schedule. The data, both from the French study and from compilation of the literature indicate, beyond reasonable doubt that the duration of counting has a direct influence on the number of kicks perceived. The shorter the counting time, the greater the number of kicks perceived per hour. Despite the exceptionally high order of magnitude of this variation is has not yet been reported as such. Biophysical profile (BPP): On the other hand, the use of Manning score may well be one of the most performing tests to decide, in presence of chronic fetal distress, whether to let the pregnancy continue or to intervene. Unfortunately, despite the excellent reports from the literature, there is not as yet a sufficiently large randomised trial of BPP in impaired fetal growth. This may well be because BPP requires a skilled ultrasound scanner and lasts on average 20 minutes. In most countries this is a double deterrent, especially where fee for service is the usual mode of retribution and BPP cannot be billed differently from a standard USS.
D. Sturdee, Department of Women's Health, Solihull Hospital, UK
Official panel discussions / European Journal of Obstetrics & Gynecology and Reproductive Biology 86 (1999) 53-58
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and Europe, and is becoming increasingly popular due to the improved long term compliance. The main purpose and benefit of the continuous progestogen is the prevention of period-type bleeds, which can be achieved in at least 75% of postmenopausal women, and higher proportions of older women. Persistent or new bleeding in women established on CCT is often associated with the finding of an endometrial polyp or submucous fibroid. An atrophic endometrium is produced and maintained in about 90% of women, and hyperplasia without atypia has rarely been reported. There have been no reports of endometrial carcinoma developing in women from a normal endometrium while taking CCT. Furthermore, a large UK study reported that when complex endometrial hyperplasia was found in women taking standard sequential oestrogen/progestogen regimens, this was converted to normal by CCT. The continuous progestogen does not prevent the beneficial effects of oestrogen on the lipid profile. On-going randomised placebo-controlled studies of secondary prevention of coronary heart disease using CCT regimens, will determine the extent of benefits for cardiovascular disease. New low dose combinations with Img oestradiol or equivalent seem to be as effective in symptom control and prevention of osteoporosis, and arc associated with fewer side effects and bleeding. They will be particularly suitable for older postmenopausal women.
Hormone replacement therapy (HRT), given as unopposed oestrogens as well as combined oestrogen-progestogen replacement, has been associated with a 40-60% reduced risk of developing cardiovascular disease in postmenopausal women. Also experimental studies in animals and humans have demonstrated the anti-atherogenic effects of HRT. The cardiovascular protection of HRT probably results from changes in a variety of risk markers, of which the number is still growing. HRT has been reported to beneficially influence e.g. the lipids and lipoproteins, depending however on the formulation's dosages, the route and duration of administration, and the type of progestogen. The contribution of modulating conventional lipids to cardiovascular protection has been estimated to be about 25%. Other potential mechanism related to HRT induced risk reductiuon are effects on: I) lipoprotein(a); 2) LDL-oxidation; 3) coagulation and fibrinolysis; 4) glucose metabolism; 5) endothelial factors; 6) homocysteine metabolism; 7) impedance to (peripheral) blood flow, and 8) cardiac function. Many, but not all, effects reported so far of HRT on these new markers are beneficial from the cardiovascular point of view. This presentation will discuss some of these mechanisms in more detail.
3. Women's health in Lund area (WHILA) study
Panel Discussion 4 - Can we minimize surgical techniques in urogynaecology
G. Samsioe, J. Lidfelt, L. Holmdahl, C. Nerbrand, B. Schersten, L. Lindholm and C.D. Agardh, Lund Universiy Hospital, Lund, Sweden The WHILA cohort aims at recruiting all women (n= 10.890) living in Lund area and born between 1935 and 1945. A questionnaire comprising 103 questions is mailed together with an invitation to undergo a healthscreening programme. At the Health Care Centre all women are personally interviewed by a specially trained nurse midwife and the basic questionnaire discussed. Interview results in changes in about 19% of the questionnaires. At this interview a second questionnaire is given to some women dependent on the answers to certain questions. A laboratory test is carried out comprising a serum lipid profile, bone mass measurement, blood pressure, waist-hip ratio and body mass index. In addition, extra blood samples are drawn and serum are stored in 5 aliquots in -70 freezes together with I aliquot of white blood cells in order to perform specific analysis of various factors which are optional. Should laboratory values fall outside certain limits, a secondary screening procedure is performed, which among other things comprises duplicate oral glucose tolerance tests with concomitant insulin determinations, thyroid function, ECG, fasted serum lipoprotein profile, HbAlC and microalbuinuria. Out of 7,200 women investigated first, II % were premenopausal (Plvl-group), 55% postmenopausal without HRT (PMT-group) and 34% postmenopausal with HRT (PMT-group). Of the latter 83% were current users. Furthermore, 19% were overweight (BMI>28) and 11% obese (BMI>30). A fasting 2 hour 75 g oral glucose tolerance test (OGTT) was performed in 1.227 women who had a 'positive' primary screening. Of these women (7%) had an impaired glucose tolerance and 1.3% had overt diabetes hitherto undiagnosed. There was a positive statistical assoiation between the random blood glucose and BMI, waist-hip ratio (p<0.02), systolic blood pressure (p
4. Mechanistic aspects of cardiovascular protection by hormone replacement therapy MJ. van der Mooren. Project 'Ageing Women' and Institute for Cardiovascular Research, Department of Obstetrics and Gynaecology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands
1. TVT-procedure Carl Gustav Nilsson, Finland
TEXT NOT AVAILABLE.
2. Traditional procedures E. Petri, Chief Dept. Obstetrics & Gynecology, Schwerin Medical School, Germany Introduction: Over the decades there have been described more than 200 different surgical procedures, modifications and submodifications for the treatment of female urinary incontinence. Gynecologists still tend to the vaginal procedures in their belief of anatomical reconstruction being the major aim of cure of sphincter incompetence. Prospective and controlled randomised studies in recent years have been able to demonstrate superiority of abdominal approaches. Surgical concept: There are two pathophysiological concepts for the approach: I. repositioning of the prximal urethra back into the abdominopelvic pressure transmission zone (e.g. colposuspension or slings); 2. Refixation of torn ligaments to the mid-urethra (TVT). Colposuspension as first described by BURCH and modified by many others has merged to be the gold-standard, giving good long-term results subjectively and objectively in follow-ups up to more than 20 years between 60-80%. We performed more than 1800 modified colposuspensions since 1985 reaching cure rates in a follow-up of up to 12 years in primary cases between 80 to 88%, 71% in recurrencies. In detailed follow-up of subjective data we had to learn that complete satisfaction of the patients in spite of complete continence is reduced by obstructive micturition and particularly in hard working women of pain in the area of fixation ('colposuspension-syndrome'). But, these symptoms should be the same in endoscopic techniques. In hypotonic urethra (lSD) and repeated recurrencies so far we performed a fiscal sling procedure in the technique described by NARIK and PALMRICH. Fairly good success rates were accompanied by an important rate of complications like obstructive voiding up to retention, secondary urgency, hernias and pain. We are changing at the present time to the tension free vaginal tape (TVT). Therapeutical strategy: After exhausting all conservative regimens including estrogen replacement, physiotherapy, cones and electrotherapy and, after urodynamic and morphologic proof of sphincter incompetence the aim of surgical therapy should be reconstruction of clinically relevant and symptomatic pelvic floor defect together with either are-positioning of the bladder neck back into the abdomino-pelvic equilibrium, in the future perhaps waiting for scar tissue fixation by TVT.
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Official panel discussions I European Journal of Obstetrics & Gynecology and Reproductive Biology 86 (1999) S3-S8
3. Laparoscopic procedures
J.M. Lavin, Dept. of Urological Gynaecology, St. Mary's Hospital, Manchester, UK Advances in imaging and instrument design has enabled surgeons to perform standard operations laparoscopically. The aim is to reproduce the results of the standard procedures but with the perceived advantages of minimal access surgery. Laparoscopic colposuspension was first reported in 1991 and since that time there have been many series reported in the literature, however, the patient selection, technique employed and follow up have not been consistent. In the majority of series, there has only been short term subjective follow up data available. Laparoscopic paravaginal repair, vault suspension and posterior vaginal wall support have all been reported. This talk will critically review the published data on laparoscopic procedures for the treatment of urogynaecological disorders.
Results: The cross-sectional study showed that steroid therapy was associated with the thinnest skin measurements (0.83 mm) obtained for all patients screened at the menopause clinic. Similarly, low bone density measurement, lumbar spine (0.81 g/cm)", hip (0.71 g/cmj" were obtained for patients on long term standing therapy. Twelve women had sustained single or multiple fractures. Since the establishment of the bone density unit 38 patients who had been on long term steroid have been followed up after the administration of oral hormone replacement therapy [Prempak C 0.625 mg]. This longitudinal study revealed a constant increase in skin thickness [6% per year] and bone density [left hip 5%, lumbar spine 4%].
3. Preventive care in breast cancer M. Birkhauer, Head, Div. of Gynaecological Endocrinology, UniversitdtsFrauenklinik Bern, Inselspital, Schanzeneckstrasse I, CH-30I2 Berne, Switzerland
Preventive care in breast cancer consisted until now mainly in regular clinical and paraclinical examinations of the breast:
4. Comparative studies of old and new techniques
Paul Hilton, UK TEXT NOT AVAILABLE.
Panel Discussion 5 - Women's Health Care 1. Cardiovascular disease in women and preventive care
G. Samsioe, Dept. of Obstetrics & Gynecology, Lund University Hospital, Lund, Sweden A growing body of evidence suggests that oestrogen replacement therapy is beneficial for women's risk of osteoporotic fractures and heart disease. A woman at 50 carries about a 50% risk of coronary heart disease and a 30% risk of dying from it. Oestrogen monotherapy greatly reduces the risk of several cardivascular manifestations, such as myocardial infarctions and stroke by approximately 50% in primary preventative trials. Even if confounding and bias are present in observational studies a randomised clinical trial may alter the exact relative risk but it is not likely to afflict the concept of cardioprotection by ERT. Angiographic studies reveal that women with the most severe stenosis are those who have the most to gain from oestrogen therapy. It can be inferred from these studies that the two major mechanisms for cardioprotection are direct effects on vessel wall leading to a vasodilatation and reduced arteriosclerosis formation. Reasons for atherosclerosis are multifold, but serum lipid and lipoprotein metabolism is considered to play a pivotal role in this respect. Oestrogens can be shown to increase HDL, lower total and LDL cholesterol and lipoprotein (a) as well as to be an antioxidant. The addition of a progestogen lowers HDL and triglycerides and further lowers total and LDL cholesterol and lipoprotein (a) and has no impact on antioxidant effects. Albeit limited, observational studies on combined hormone therapy agree that there is no attenuation by the addition of a progestogen to oestrogen regardless of the nature of the progestogen. 2. Primary and preventive osteoporosis care
M. Brincat, Y. Muscat Baron, R. Galea. Departent of Obstetrics and Gynaecology, University of Malta, Medical School of Malta, Msida, Malta Introduction: Long term steroid therapy is complicated by osteoporosis and generalised thinning of the skin. These two complications of long term steroid therapy are routinely assessed at the menopause clinic of St. Luke's Hospital. Patients and methods: A cross-sectional study was performed on 164 postmenopausal women who had been on long term corticosteroid therapy. A longitudinal study on 38 postmenopausal women on long term steroid therapy was performed. Each women had the skin thickness measured by high resolution ultrasound (22 MHz) and the bone density measured by a DEXA-Norland 386.
• annual clinical examination of the breast • mammography and/or sonography every two years in the normal population, every year in high risk patients Recently, the preventive administration of antihormones or SERM's (Selective Estrogen Receptor Modulators) has been proposed in high risk patients, based on preliminary data obtained with Tamoxifene and Raloxifene. A first study using Tamoxifene resulted in a lower incidence of breast cancer in the Tamoxifene group, suggesting a reventive effect of SRM's. However, these data have not been confirmed by two other studies. The preliminary data obtained in the Raloxifene trials are encouraging. Although they are based on a relatively low number of cancers, a preventive effect on breast cancer is likely. However, there are no data on mortality in women having received a preventive administration of SERM's. SERM's could select receptor-neg. tumours and therefore more aggressive cancers. Before general recommendations can be made, the risks and the benefits of a preventive administration of SERM's have to be thoroughly evaluated by large additional prospective trials
4. Estrogens may prevent CNS diseases in women
Manuel Neves-e-Castro, Av. Antonio de Aguiar, 24, 2° D, 1050-016 Lisbon, Portugal It is now well established that the brain is a target for sex steroidal hormones trough genomic and non-genomic mechanisms of action. Experimental studies indicate that estrogen deprivation causes a decrease in brain neuro transmitters and that estrogens can reverse such changes. Post-menopausal women often suffer from brain disfunctions that may cause mood changes, decreases in cognition and memory, etc. Estrogen replacement may improve such disorders in many women suggesting that these hormones have an effect in brain organization. Furthermore, estrogens maintain brain circulation and have pronounced effects in lipoprotein metabolism, thus contributing to a better brain function. There is growing evidence that estrogens given to postmenopausal women may decrease and ameliorate their symptomatology. Therefore, hormone replacement therapy given to postmenopausal women has positive effects on CNS derived symptoms, in the short term, and may have preventive actions in the long term.
Panel Discussion 6 - Long term consequences of infertility treatment for mother and child 1. Complications of induction ovulation
J. Schenker, Israel TEXT NOT AVAILABLE.
Official pa nel discuss ions I European Jou rnal of Obstetrics & Gynecolo gy and Reproductive Biology 86 ( 1999) 53 -58
2. Genetic risks of IVF/ICSI Madalena Barata, Campo Grande 30. l 'T), Po rtugal Mushin in 1985 published on Clin. Obstet. Gynaecol., a ration ale for the study of IVF children. The focus of this paper was to determine whether or not a significant risk involving these children. Hurst from Syndey in 1997 presented figures for 1979-1995, showing 2.5% of infants and foetuses with major congeni tal malformations. This rate in the normal population is similar. Concerning long term follow-up of a large series of children born after ICSI, at this time there is none. However, genetic defects associa ted with male fertility pro blems can be transmitted to offspring. E. Legins group from the centre for Human Genetic s, Gasthuisberg, Leuven started a prospective study of 388 males with fertili ty problems. Chromosomal abnormalities, mutatio ns in the cystic fibrosis gene, and microdeletions on the Y chromosome are in analysis .
3. ART and gynecological malignancies
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4. Health of the children conceived with IVF/ICSI F. Olivennes, France The first IVF children are 20 years old. Since then, major progress has been made in various aspects of IVF and the number of children conceived with the help of IVF is incre asing. Very few reports have been published on the long-term follow- up of IVF children. Most of these studies are presenting reassuring data , but the methodology of nearly all of them do not allow to conclude that IVF has no detrimental effect on the grow th and on the motor and psycho logical development of the children conceived with this technique. The differe nces existing betwee n fertile and infertile couples make the pediat ric follow-up studies very difficult to organise , especially for the choice of a control group. The major difficulties are the number of children to be included, the type and exte nt of evaluation, the length of the follow-up, the risk of high rate lost for follow-up. There is also a clear ethical problem to singularise IVF children by enrolling them in specific medical and psychological studies. However, the evaluation of the assisted reproductive technologies is mandatory, and the well-being of the children has to be evaluated especially with the new techniqu es used with gametes and embryos.
P.N. Barri, M. Izquierdo, B. Corole u, Service of Reproductive Medicine, Depa rtment of Obstetrics and Gynaecology , Institut Universitari Dexeus, Barcelona, Spain The aetiology of many gynaecological cancers is, even today. poorly understood. It is known that women who have no had children run a higher risk of cance r of the breast, of the ovary and of the endometrium, a close relationship having been established betwee n the age of the first birth and the risk of cance r of the breast. Although the greater risk of gynaecological cancer in childless women appears to be due to the fact of their involunary infertility and the logical absence of known protection factors such as multiparity and lactati on, it is incumbent upon us to deepe n our knowledge of the risks additional to those to which involuntarily infertile patient may be subjected. Present-day Assisted Reproduction technciques, with their usual protocols of stimulation of follicular develop ment by means of drugs such as clomiphene citrate and the gonadotrophins, have been suggested as possible additional riks factors in infertile patients with respect to cancer of the breast, ovary and endometrium. We have evalu ated the incide nce of gynaecological cancer among the first 900 patients who underwent ovarian stimulation with a view to IVF in our Institute and who were followed up for more than 10 years (7,917 years of follow-up). Among these patients we found 2 cases of breast cancer and I case of ovarian cancer. At the same time we analysed the data of a historical group of 5 patients from our Service of Reprodu ctive Medicine and not included above who presented a gynaec ological cancer in their follow-u p. The first evalua tion which we must make is epidemio logica l, bearing in mind the expected incidence and that encountered in our sample with regard to the protection and risk factors presented by the patients included in the follow-up . We took as a standard or reference population the population of the province of Tarrago na and their cance r register during the period 1984-1 987. From these data we obtained an estimat ion of the expected cases taking as a starti ng point the specific levels of incidence by age and sex from this register. According to our data in our study population 2.3 cases of breast cancer, 1.08 cases of ovarian cancer and 2.1 cases of endometrial cancer should have been expected. The observation of 2 breast eancers and one ovarian cancer does not supply us with standard ised Morbidity Indices (S.M.!.) which are lower than unitr, which leads us to think that we have not observed more cases than would have been expected. Great care must be taken in analysing all these data since some of the diffe rences observed between the groups may be due to what are still very prelimi nary results which may be affected by some statistical anomaly. For this reason this study remains open to include more patients and extend their follow -up. Continued study of a large number of cases may change some of the tendencies or confirm others. We must not forget the risk factors which these patients have by virtue of being inferti le. In our study we have not been able to discern differences with respect to the post-treatment pregna ncy of the two groups We shall probably reach the conviction that much wider multi-centre studies will be needed in order to draw definitive conclus ions.
EBCOG Training Session - Training in obstetrics and gynaecology 1. EBCOG's recommendations on tra ining Jacques Lansac, France TEXT NOT AVAILABLE.
2. Quality control J.W. Wladimiroff, Department of Obstet rics & Gynaecology. University Hosp ital Rotterdam-Dijkzigt, Rotterdam, The Netherlands Since EBCOG came into being in September 1996, the organisation has made considerable progress both in its working parties and its relations hip with other organisations, such as EAGO . One of the Working Parties is the Hospital Visiting Committee which aims at ensuring quality contro l of specialist training of its training units in Europe. Up until now, 16 academi c centres have been visited in countries like Norway, Slovenia, Germany, Portugal, France, Spain, The Netherlands and Hungary . The visits, so far, are considered very succe ssful by both the visitors and visited. Emphasis lies on the training system which includes the presence of a struct ured training programme , sufficient training facilities, adequate theoretical training, a tutorial system and continuo us assessment of practical skills and theoretical knowledge. It has become clear that in some countries national labour policies have a direct impact on the quality of traini ng. Thi s implies that EBCOG - through the UEMS should have access to sending the recommendations coming out of the visits to a higher health care level (Ministry of Health) in the host country . Struct ured revisits should take place every five years. Natio nal societies should take over the visiting process after 5- 10 visits to the host country pending on the acquisi tion of sufficient experience in the visiting process and the implementation of a well-organised national visiting system.
3. Training In obstetrics and gynaecology - the trainees opinion Filome na Nunes , President of the European Netwo rk of Trainee s in Obstetrics and Gynaec ology
In 1975 the European Union of Medical Specialists , participated in the definition of the European Medical Directives, that regualte the free movement of doctors and mutual recog nition of medical credentials, throughout the European Communi ty. Training in Obstetrics and Gynaecology in Europe is still quite heterogeneous reflecting the cultural, social and ethical differences .
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Official panel discussions I European Journal of Obstetrics & Gynecology and Reproductive Biology 86 (1999) 83-88
Nevertheless many countries do seem to be approaching a standard, for example the duration of training is now fairly uniform. The definition and recommendations on what is basic and should be common to all countries will help to achieve quality control in training. Quality control in training: training programs, training centres, trainers and trainees. The European Network of Trainees in Obstetrics and Gynaecology (ENTOG) was created in 1996, to establish communication and represent the European trainees. The aims of ENTOG are to promote a better understanding of training in Obstetrics and Gynaecology in Europe thus ensuring comparable and high standards of training.
The position of the European Board and College of Obstetrics and Gynaecology working in co-operation with the National Authorities of each country and the trainees was an important step to allow the establishment of common European Recommendations for training. It is unlikely that complete harmon isation of training in Obstetrics and Gynaecology is possible in Europe. However, it is hoped that if the EBCOG recommendations are implemented by all Europe an countries then a certain quality of training will be assured.