Informed consent to undergo serum screening for Down's syndrome: the gap between policy and practice.
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Communication↗
Biomedical subjects
R W Shaw
Publications and source records attributed to R W Shaw.
A randomized, double-blind, placebo-controlled study of luteal phase dydrogesterone (Duphaston) in women with minimal to mild endometriosis.
OBJECTIVE: To compare dydrogesterone with placebos in the treatment of minimal to mild endometriosis. DESIGN: Prospective, double-blind, randomized study. SETTING: Three Obstetrics and Gynaecology Departments in the United Kingdom. PATIENTS: Sixty-two premenopausal women with complaints of pain (n = 12) and infertility with or without pain (n = 50) with minimal to mild endometriosis diagnosed at laparoscopy. Thirty-nine women had a laparoscopy after treatment and 56 women were followed up 12 months after treatment. INTERVENTIONS: Two high doses of dydrogesterone (either 40 or 60 mg) or a placebo, which was given for 12 days, beginning 2 days after the LH surge for a treatment period of 6 months. MAIN OUTCOME MEASURES: Change between before and after treatment endometriosis scores, pregnancy rates (PRs), and pain. RESULTS: Treatment with dydrogesterone did not alter the natural history of endometriosis or PRs when compared with placebo. Pain was reduced significantly during treatment with 60 mg dydrogesterone and this improvement still was evident at 12-month follow-up. CONCLUSION: Luteal phase dydrogesterone reduces pain associated with endometriosis.
Adult↗
Morphology and ultrastructure of fallopian tube epithelium at different stages of the menstrual cycle and menopause.
The Fallopian tube has been reported to undergo cyclical changes. However, many studies of tubal ultrastructure have either examined one segment of the tube only or studied animal oviducts. The aim of this study was to document in detail the combined morphological and ultrastructural features of the epithelial lining along the length of the tube in women at different stages of the menstrual cycle. We report an increase in the proportion of ciliated cells along the tube, being highest in the fimbriae, but no substantial difference between the follicular and luteal phases of the menstrual cycle. In the late follicular phase, fragments of cytoplasmic and cellular material were seen in the isthmic lumen but not in the outer tubal segments. Similarly, surface domes and secretory granules were more prominent in the mid-tube and ampullary sections than in the fimbriae. This surface activity was followed by relative quiescence in the early/mid luteal phase with reversion to a more active surface but with little secretory activity in the late luteal phase. These findings along the Fallopian tube substantiate the concept of functional differentiation between the different segments and necessitate further studies to determine its clinical relevance.
Cytoplasmic Granules↗
A comparative morphological and ultrastructural study of endometrial gland and fallopian tube epithelia at different stages of the menstrual cycle and the menopause.
Cyclical ultrastructural changes in the endometrium and Fallopian tube have been reported previously but in different subjects. The aim of this study is to compare cyclical changes in endometrial gland and tubal (isthmic, mid-tube, ampulla, and fimbria) epithelia in the same subjects with a view to identifying any similarities or differences which may have clinical implications for assisted reproduction treatment. Endometrial and Fallopian tube samples were obtained from women undergoing hysterectomy and salpingectomy. We report similar epithelial surface changes taking place in the endometrial glandular and endosalpingeal epithelia with the exception of the fimbriae. Secretions within endometrial gland lumen and the isthmus increase throughout the late follicular phase and before ovulation, then dissipate in these two regions simultaneously in the early/mid luteal phase. Similarly, in the late follicular and pre-ovulatory phases, the process of granule secretion is similar in the glandular epithelium, isthmus and ampulla. In the fimbriae, no comparable activity is noted during these phases of the menstrual cycle. The differences reflect the functional differentiation between these regions. Equally, the observed similarities highlight the need for further comparative studies to determine the role of these secretions in early embryonic development and their clinical relevance.
Cytoplasmic Granules↗
Comparative immunohistochemical study of oestrogen and progesterone receptors in the fallopian tube and uterus at different stages of the menstrual cycle and the menopause.
Oestrogen and progesterone are known to require their corresponding steroid receptors to manifest structural and functional effects in the Fallopian tube, uterus and other target organs. This study compares cyclical variations of these receptors in the uterus and in different segments of the Fallopian tube in the same subjects using an immunocytochemical technique. The results show that in the Fallopian tube, isthmic and ampullary epithelial and stromal oestrogen receptors increased in the follicular phase to a peak at mid cycle and then declined in the late luteal phase. The intensity of immunostaining of oestrogen receptors was less in the Fallopian tube than in endometrial glandular epithelium. The fimbrial end demonstrated an opposite pattern of staining to other segments of the tube. Progesterone receptor immunostaining was more intense than that for oestrogen receptors in the follicular phase, and, whereas it disappeared completely from the endometrial glandular epithelium in the late luteal phase, positive staining was clearly visualized in the tubal epithelium and stroma and endometrial stroma at this stage of the menstrual cycle. These differences in the steroid receptor content may reflect the changing and different functional roles of these regions and may have important implications on human reproduction.
Endometrium↗
Assessment of medical treatments for menorrhagia.
Although usually not life-threatening, dysfunctional uterine bleeding (DUB) can cause discomfort and disruption to life for many women. It has been poorly researched in the past, primarily because of difficulties in trying to accurately measure blood loss and response to treatment. There are several different therapies currently available but, for many, actual evidence of their efficacy is lacking from scientific data. Progestogens are the most frequently prescribed drugs for the treatment of DUB. Data support their use in anovulatory women but a number of comparative trials have shown that an overall reduction in blood loss of only 20% is achieved in ovulatory women. Their use, therefore, must be questioned as the first line of treatment. Combined oral contraceptives were at one time popular but whether the low-dose, current generation pills are equally effective awaits appropriate trials. Prostaglandin synthetase inhibitors can be useful, with up to a third of women with menorrhagia benefiting from a reduction of between 25% and 35% in blood loss. A proportionally greater reduction is seen in women with more excessive bleeding. Antifibrinolytic drugs have been shown to reduce menstrual blood loss in DUB by 50% and would be useful in women in whom oestrogens are contraindicated. Gonadotrophin-releasing hormone analogues are highly effective because of their ability to induce amenorrhoea, but long-term use is contraindicated because of their hypo-oestrogenic effects. One other effective therapy for menorrhagia has been danazol.(ABSTRACT TRUNCATED AT 250 WORDS)
Anti-Inflammatory Agents, Non-Steroidal↗
Lack of knowledge in health professionals: a barrier to providing information to patients?
OBJECTIVE: To assess obstetricians' and midwives' knowledge of routine prenatal screening tests for fetal abnormality and factors associated with such knowledge. DESIGN: Questionnaire assessment of antenatal clinic staff. SETTING: Six hospitals within the United Kingdom (four district general hospitals in London, one district general hospital in Wales, and one teaching hospital in Wales), offering routine prenatal screening tests. SUBJECTS: 29 obstetricians and 97 midwives were invited to participate, of whom 21 and 70 respectively responded to the questionnaire. MAIN MEASURES: Knowledge of prenatal tests, according to 19 item multiple choice questionnaire, reluctance to disclose uncertainty, and clinical experience. RESULTS: The overall response rate was 72% (91/126). In all, 43% of midwives and 14% of obstetricians obtained correct responses on fewer than half the items. Reluctance to disclose uncertainty to patients was associated in obstetricians with having less knowledge about prenatal testing (r = -0.50; p < 0.025, Pearson product moment correlation) and in midwives with more clinical experience (r = 0.43; p < 0.001). CONCLUSIONS: Lack of knowledge and greater clinical experience seem to be important barriers to providing patients with information about prenatal screening tests.
Communication Barriers↗
A risk benefit assessment of drugs used in the treatment of endometriosis.
Medical treatments of endometriosis rely upon the hormonal dependence of endometriotic implants for further growth and extension. The cyclic nature of the symptoms means they may be helped by agents that suppress menstruation both from the endometrium and within the endometriotic lesions. In comparative trials, progestogens have been shown to achieve a similar reduction in symptoms and to induce regression of deposits, but to date there are few long term follow-up data concerning gestrinone. The recent introduction of gonadotrophin-releasing hormone (GnRH) agonists, highly effective at inducing a state of sustained hypoestrogenaemia, is providing another group of compounds suitable for use in the treatment of endometriosis. In comparative trials with danazol, a number of these compounds administered in novel formulations (as intranasal sprays or sustained release depots), have been shown to significantly reduce symptoms both during treatment and for 6 to 12 months post-treatment when compared with baseline. In addition, there are highly significant reductions in revised American Fertility Society (R-AFS) total and implant alone scores following 6 months' therapy. Whilst these changes are not significantly different from danazol, there are fewer patients discontinuing treatment with GnRH agonists than with danazol. The low circulating levels of 17 beta-estradiol seen during GnRH analogue therapy result in alterations of bone mineral metabolism similar to those observed at the menopause. Continued prolonged use would thus result in reduced bone mass and this factor will limit the duration of use of GnRH agonists long term until appropriate combination ('add-back') regimens to protect bone are developed.
Cyclooxygenase Inhibitors↗
A prospective randomized crossover comparison of zygote intrafallopian transfer and in vitro fertilization-embryo transfer in unexplained infertility.
60 couples aged under 38 with unexplained infertility were recruited in this prospective randomized crossover study to compare the efficacy of treatment between ZIFT and IVF-ET. A total of 150 stimulation cycles were commenced and 132 proceeded to successful egg collection (88%). Fertilization successfully occurred in 114 cycles (86.36%). A total of 110 embryo replacements were carried out, (52 uterine transfer and 58 tubal transfer). This prospective randomized cross over trial demonstrated the trend for higher implantation rate, pregnancy rate, and ongoing pregnancy rate with ZIFT over IVF-ET for patients with unexplained infertility. The actual implantation rate, pregnancy rate, and ongoing pregnancy rate with ZIFT were 13.7, 34.5, 31.0 per cent respectively compared to the results from IVF-ET which were 12.1, 26.9, 25.0 per cent respectively. However, the difference was not statistically significant. Although this study showed a 5 per cent ectopic pregnancy rate with ZIFT and none with IVF-ET, the difference was not statistically significant. Similarly, there was no difference in the overall miscarriage rate and multiple pregnancy rate between the two protocols. In conclusion, this prospective randomized crossover trial demonstrated the trend for higher reproductive outcomes in term of implantation rate, pregnancy rate, and ongoing pregnancy rate with ZIFT over IVF-ET in unexplained infertility but the difference was not statistically significant.
Adult↗
Treating the patient with menorrhagia.
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Female↗
Pretreatment with gonadotrophin releasing hormone (GnRH) analogue prior to in vitro fertilisation for patients with endometriosis.
To assess the effect of GnRH pretreatment prior to IVF-ET on fertilisation and pregnancy rates in patients with endometriosis compared with tubal infertility, a retrospective analysis of 228 cycles of tubal infertility cases (Group 1) and 92 cycles of endometriosis has been performed. Patients with endometriosis were classified by the revised AFS scoring system to two groups: 37 cycles of minimal and mild endometriosis (Group 2) and 55 cycles of moderate and severe endometriosis (Group 3). The GnRH analogue buserelin was used for pituitary desensitisation in all IVF cycles. Endometriosis patients have a minimum of 6 weeks GnRH treatment prior to superovulation therapy. Although the fertilisation rate per oocyte (51%) was significantly lower in Group 3 (P < 0.001), the percentage of cycles in which fertilisation occurred (86%, 78%, 78%) and the pregnancy rates per embryo transfer (17.7%, 17.2%, 18.6%) for Groups 1, 2 and 3, respectively, were not significantly different. Pretreatment with GnRH analogues allows patients with endometriosis to achieve similar success rates to patients with tubal infertility alone.
Adult↗
Ovarian 11 beta-hydroxysteroid dehydrogenase: potential predictor of conception by in-vitro fertilisation and embryo transfer.
Cortisol is converted to the inactive glucocorticoid, cortisone, in several tissues by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). We have recently measured 11 beta HSD activity in cultured human granulosa-lutein cells recovered from patients undergoing in-vitro fertilisation and embryo transfer (IVF-ET). We now report an association between the outcome of IVF-ET and 11 beta HSD activity in these cells. Of the 64 patients studied, 32 had detectable 11 beta HSD activity and none became pregnant; whereas 76% of the remaining "11 beta HSD-negative" patients achieved pregnancies. Hence 11 beta HSD activity may predict the outcome of IVF-ET.
11-beta-Hydroxysteroid Dehydrogenases↗
A comparative study of danazol, a regimen of decreasing doses of danazol, and norethindrone in the treatment of objectively proven unexplained menorrhagia.
OBJECTIVE: Our purpose was to compare the efficacy of the recommended dose of danazol, a reduced-dose danazol regimen, and norethindrone in the treatment of objectively proven menorrhagia. Recurrence after discontinuing treatment was also assessed. STUDY DESIGN: The study was a single-blind, randomized, parallel, comparative study. After a placebo run-in period over two menstrual cycles, 57 patients with a baseline mean menstrual blood loss of at least 80 ml per cycle were randomly assigned to receive one of three therapies: danazol, 200 mg/day (n = 19) for three menstrual cycles; danazol, 200 mg/day for one cycle, 100 mg/day for one cycle, and 50 mg/day for one cycle (n = 19); and norethindrone, 5 mg three times daily on days 19 through 26 of the cycle for three consecutive cycles (n = 19). Patients in whom treatment was successful (those experiencing blood loss < 80 ml) were entered in the follow-up phase of the study, receiving placebo for a maximum of four menstrual cycles. RESULTS: The final menstrual blood loss on treatment was significantly less for those patients who received both danazol regimens compared with those who received norethindrone (p = 0.017 for reducing dose danazol vs norethindrone and p = 0.043 for 200 mg of danazol vs norethindrone). Both danazol treatment regimens were significantly more successful in reducing menstrual blood loss to within the normal range than was norethindrone. The reducing-dose danazol regimen was successful in eight of 17 patients (p = 0.027), and 200 mg of danazol was successful in nine of 19 patients (p = 0.029), compared with the two successes of 18 patients treated with norethindrone. Significantly more recipients of 200 mg of danazol than of norethindrone subjectively rated their treatment to be moderately or highly effective (p = 0.033). Both danazol treatment regimens were associated with a higher incidence of adverse events than was norethindrone therapy, although the number of withdrawals were similar and infrequent in the three groups. CONCLUSIONS: Both danazol regimens were significantly more effective than norethindrone in reducing the excessive menstrual blood loss of women with unexplained menorrhagia. A subjective assessment by patients found that only the 200 mg of danazol was judged to be significantly more effective than norethindrone in controlling the heaviness of menstrual bleeding. The reduced-dose danazol regimen did not appear to markedly diminish the incidence of adverse events compared with the 200 mg of danazol regimen.
Adult↗
The prevalence of endometriosis in women with infertile partners.
Laparoscopy was performed on a consecutive series of 174 women complaining of infertility. Forty of these women were the partners of oligospermic or azoospermic men. There was no difference in the prevalence of endometriosis between those women whose partners were fertile and those whose partners were infertile. Women with azoospermic partners had a prevalence of endometriosis of 20.7%, and this is likely to reflect the true prevalence of endometriosis in a group of randomly selected normal women.
Adult↗
Gonadotropin-releasing hormone analogues for the treatment of endometriosis: long-term follow-up.
OBJECTIVE: To determine the long-term recurrence rate of endometriosis after treatment with gonadotropin-releasing hormone analogues (GnRH-a). DESIGN: A historical prospective study. SETTING: Royal Free Hospital, London, a tertiary referral center for the treatment of endometriosis. PATIENTS: One hundred thirty patients with endometriosis had treatment with GnRH-a buserelin acetate, goserelin, and nafarelin acetate between the years 1985 and 1987. Patients no longer being followed in the gynecology clinic were sent a questionnaire to determine their state of health. Information was also requested from the patient's general practitioner. MAIN OUTCOME MEASURES: The cumulative recurrence rate for the fifth year after treatment ended was 53.4%. RESULTS: Patients with a higher disease stage at the outset were more likely to experience recurrence and experience it earlier than patients with minimal disease. Fifth-year recurrence rates were 36.9% for minimal disease and 74.4% for severe disease. The change in endometriosis stage classification scores at second-look laparoscopy for those patients whose disease recurred after treatment was not significantly different from those whose disease did not recur during the study period. CONCLUSIONS: Patients with endometriosis treated with GnRH-a are highly likely to suffer a recurrence of their disease, particularly if their disease is severe at the outset.
Adolescent↗
A randomized comparative study of the metabolic effects of two regimens of gestrinone in the treatment of endometriosis.
OBJECTIVE: To study some of the metabolic effects of oral gestrinone on plasma lipoprotein risk markers for cardiovascular disease and on bone density, a risk marker for osteoporosis. DESIGN: Randomized double-blind study. SETTING: All patients were referred to Gynaecology Clinic of Royal Free Hospital Medical School. PATIENTS: Twenty premenopausal women with laparoscopically confirmed endometriosis. INTERVENTIONS: Subjects were randomized in a double-blind fashion to receive either 1.25 mg or 2.5 mg gestrinone two times per week for 6 months. MAIN OUTCOME MEASURE: Laparoscopy was performed before treatment, and clinical responses were determined by second laparoscopy after 6 months. Plasma lipid and bone density measurements during and after therapy were compared with baseline. RESULT: Median total endometriosis scores decreased from 7.5 to 1.0 in the 1.25-mg group and from 7.0 to 0 in the 2.5-mg group. There were no significant between-group differences in endometriosis scores. At both doses, bone density in the spine and the proximal femur was conserved, but plasma concentrations of low-density lipoproteins rose by 13% and those of high-density lipoproteins fell by 40%. CONCLUSIONS: Reducing the dose of gestrinone to 1.25 mg appeared to maintain the therapeutic effectiveness of this treatment but was still associated with potentially unfavorable effects on lipids and lipoproteins.
Adult↗
A critical appraisal of assisted reproduction techniques.
Several treatments for infertility have been promoted with only little supporting objective data demonstrating their therapeutic value. The choice of an assisted reproductive technique depends on a balance between numerous factors. Seldom is the choice absolute as in patients with tubal block. There is conflicting evidence on the efficacy of simpler methods such as ovarian stimulation with or without artificial insemination and the available data suggest that the more invasive methods such as gamete intra-Fallopian transfer or in-vitro fertilization are more effective in the treatment of couples with unexplained infertility. Equally, there is no conclusive evidence that pregnancy rates with any of the invasive techniques are superior to any others. However, a higher implantation rate following tubal embryo transfers is observed in many studies. This review presents a critical assessment of the effectiveness of assisted reproductive techniques.
Embryo Transfer↗
Direct inhibition of ovarian steroidogenesis by cortisol and the modulatory role of 11 beta-hydroxysteroid dehydrogenase.
OBJECTIVE: The association of adrenal hyperactivity with ovarian dysfunction may involve direct inhibition of ovarian steroidogenesis by glucocorticoids. Therefore, the objectives of this study were to investigate the direct effects of cortisol on luteinizing hormone (LH) action in human granulosa-lutein cells and the modulation of this interaction by ovarian 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). DESIGN AND PATIENTS: Effects were investigated in cultured human granulosa-lutein cells isolated from the follicular aspirates of 14 patients undergoing oocyte collection for in-vitro fertilization and embryo transfer. MEASUREMENTS: Pregnenolone production and 3H-cortisol oxidation to 3H-cortisone (11 beta HSD activity) by cultured cells were measured. RESULTS: In cells from nine (of 14) patients, cortisol inhibited LH-stimulated steroidogenesis in a concentration dependent manner with an ID50 of 1250 +/- SEM 377 nmol/l. In these cultures, the 11 beta HSD activities were high (133 +/- SEM 23 pmol/mg protein/4h) and inhibition of the enzyme with carbenoxolone potentiated the action of cortisol. Conversely, cells from the remaining five patients lacked detectable 11 beta HSD activity and exhibited an increased sensitivity to the inhibitory action of cortisol (ID50 = 158 +/- SEM 41 nmol/l in the absence of carbenoxolone). CONCLUSIONS: Cortisol acts directly in human granulosa-lutein cells to inhibit the support of steroidogenesis by LH and this interaction is modulated by ovarian 11 beta HSD in the majority of patients.
11-beta-Hydroxysteroid Dehydrogenases↗