Cervical insemination versus intra-uterine insemination of donor sperm for subfertility.

BACKGROUND: Insemination with donor sperm is an option for couples for whom in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI) has been unsuccessful, couples with azoospermia and for single women or same sex couples. Insemination of sperm can be done via cervical (CI) or intra-uterine (IUI) routes. IUI has been considered potentially more effective than CI as the sperm bypasses the cervical mucus and is deposited closer to the fallopian tubes. The cost and risks of IUI may be higher because of the need for sperm preparation and the introduction of foreign material into the uterus. Donor sperm used for artificial insemination is mainly cryopreserved, due to concerns about HIV transmission. However, cycle fecundity is higher for fresh sperm. Insemination is often combined with ovulatory stimulation, with either clomiphene or gonadotrophin. There may be risks associated with these therapies, such as higher multiple pregnancy rates. OBJECTIVES: To determine whether pregnancy outcomes are improved using intra-uterine insemination in comparison to cervical insemination in women undergoing artificial insemination with donor sperm. SEARCH STRATEGY: The following databases were searched: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, CENTRAL (The Cochrane Library) , MEDLINE, EMBASE, CINAHL and the reference lists of articles retrieved. SELECTION CRITERIA: Randomised controlled trials comparing IUI with CI were included. Crossover studies were included if pre-crossover data was available. DATA COLLECTION AND ANALYSIS: Study quality assessment and data extraction were carried out independently by two review authors (DB, JM). Authors of studies that potentially met the inclusion criteria were contacted, where possible if additional information was needed. MAIN RESULTS: The search strategy found 232 articles. Fifteen studies potentially met the inclusion criteria. Four studies were included in this review. All the included studies used cryopreserved sperm in stimulated cycles. In two studies 134 women had gonadotrophin-stimulated cycles and in two studies 74 women had clomiphene-stimulated cycles. The evidence showed that IUI after 6 cycles significantly improved live birth rates (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.02 to 3.86) and pregnancy rates (OR 3.37, 95% CI 1.90 to 5.96) in comparison to cervical insemination. There was no statistically significant evidence of an effect on multiple pregnancies (OR 2.19, 95% CI 0.79 to 6.07) or miscarriages (relative risk (RR) 3.92, 95% CI 0.85 to 17.96). AUTHORS' CONCLUSIONS: The findings of this systematic review support the use of IUI rather than CI in stimulated cycles using cryopreserved sperm for donor insemination.

Phytoestrogens for vasomotor menopausal symptoms.

BACKGROUND: Vasomotor symptoms, such as hot flushes and night sweats, are very common during the menopausal transition. Hormone replacement therapy has traditionally been used as a very effective treatment but concerns over increased risks of some chronic diseases have markedly increased the interest of women in alternatives. Some of the most popular of these are treatments based on foods or supplements enriched with phytoestrogens, plant-derived chemicals that have oestrogenic action. OBJECTIVES: To assess the efficacy, safety and acceptability of foods and supplements based on high levels of phytoestrogens for reducing hot flushes and night sweats in postmenopausal women. SEARCH STRATEGY: Searches were undertaken of the following electronic databases: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of randomised trials, Cochrane Register of Controlled Trials (CENTRAL) (March 2007), MEDLINE (1966 to March 2007), EMBASE (1980 to March 2007), AMED (1985 to March 2007), PsycINFO (1986 to March 2007) and CINAHL (1982 to March 2007). Attempts were made to access grey literature by letters to pharmaceutical companies and searches of ongoing trial registers. Reference lists of included trials were also searched. SELECTION CRITERIA: Studies were included if they were randomised, had peri- or postmenopausal participants with vasomotor symptoms, a duration of at least 12 weeks and where the intervention was a food or supplement with high levels of phytoestrogens (and not combined with other herbal treatments). Trials of women who had breast cancer or a history of breast cancer were excluded. DATA COLLECTION AND ANALYSIS: Selection of trials, data extraction and quality assessment were undertaken by at least two authors. Most of the trials were too dissimilar to combine in meta-analysis and their results are provided in table format. Studies were grouped into broad categories: dietary soy, soy extracts, red clover extracts and other types of phytoestrogen. Five trials used Promensil, a red clover extract; these trials were combined in a meta-analysis and summary effect measures were calculated. MAIN RESULTS: Thirty trials comparing phytoestrogens with control met the inclusion criteria. Very few trials had data suitable for combining in meta-analysis. Of the five trials with data suitable for pooling that assessed daily frequency of hot flushes, there was no significant difference overall in the frequency of hot flushes between Promensil (a red clover extract) and placebo (WMD=-0.6, 95% CI -1.8 to 0.6). There was no evidence of a difference in percentage reduction in hot flushes in two trials between Promensil and placebo (WMD=20.2, 95% CI -12.1 to 52.4). Individual results from the remaining trials were compared. Some of the trials found that phytoestrogen treatments alleviated the frequency and severity of hot flushes and night sweats when compared to placebo but many of the trials were of low quality and were underpowered. There was a strong placebo effect in most trials with a reduction in frequency ranging from 1% to 59% with placebo. There was no indication that the discrepant results were due to the amount of isoflavone in the active treatment arm, the severity of vasomotor symptoms or trial quality factors. There was also no evidence that the treatments caused oestrogenic stimulation of the endometrium (an adverse effect) when used for up to two years. AUTHORS' CONCLUSIONS: There is no evidence of effectiveness in the alleviation of menopausal symptoms with the use of phytoestrogen treatments.

Chinese herbal medicines in the treatment of ectopic pregnancy.

BACKGROUND: Traditional Chinese herbal medicine (CHM) has been used widely in Chinese hospitals to treat ectopic pregnancy. Many studies have been published supporting its use but the evidence has not been systematically reviewed. OBJECTIVES: To determine the effectiveness and safety of CHM in the treatment of ectopic pregnancy. SEARCH STRATEGY: Computerised databases (CENTRAL (The Cochrane Library), MEDLINE, EMBASE, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP, Traditional Chinese Medicine Database System) were searched from their inception to March 2006 for relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCT) on the use of CHM for the treatment of ectopic pregnancy. DATA COLLECTION AND ANALYSIS: Original authors of the identified studies were contacted to determine the trial design and identify authentic RCTs. Two review authors extracted and analysed the data. MAIN RESULTS: The search identified 166 trials. Only two studies involving a total of 157 participants were confirmed to be authentic RCTs ( Li 2004c; Zhao 2000). Both were of poor methodological quality with a high risk of conflicted interest and potential for bias in favour of the intervention. We could not reach a definitive conclusion from the results. The pooled result showed that adding a Western medicine to CHM resulted in a significantly higher treatment success rate than with CHM alone (RR 1.33, 95% CI 1.08 to 1.63). When CHM plus Western medicine was compared to CHM alone for the time to disappearance of abdominal pain, again the results favoured the arm that included Western medicine (RR -2.09, 95% CI -4.14 to -0.04). Results were inconsistent for the time required for human chorionic gonadotropin (beta-hCG) to return to normal. One study favoured CHM plus Western medicine over Western medicine (with or without placebo) (WMD -6.68, 95% CI -11.49 to -1.87); when CHM plus Western medicine was compared to CHM alone the results favoured the arm that included Western medicine (WMD -8.12, 95% CI -10.89 to -5.53). AUTHORS' CONCLUSIONS: We have not found any well-designed trials investigating traditional Chinese herbal medicines in the treatment of ectopic pregnancy. We cannot support or refute any CHM preparation for clinical use on the basis of evidence from randomised controlled trials.

Laparoscopic 'drilling' by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.

BACKGROUND: Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned due to the risk of postsurgical adhesions and the introduction of medical ovulation induction with clomiphene and gonadotrophins. However, women with PCOS who are treated with gonadotrophins often have an over-production of follicles which may result in ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. Moreover, gonadotrophins, though effective, are costly and time-consuming requiring intensive monitoring. Surgical therapy with laparoscopic ovarian 'drilling' (LOD) may avoid or reduce the need for gonadotrophins or may facilitate their usefulness. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. SEARCH STRATEGY: We used the search strategy of the Menstrual Disorders and Subfertility Group. SELECTION CRITERIA: We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS who undertook laparoscopic ovarian drilling in order to induce ovulation. DATA COLLECTION AND ANALYSIS: Sixteen trials were identified and nine were included in the review. All trials were assessed for quality criteria. The primary outcomes were live birth, ovulation and pregnancy rates and the secondary outcomes were rates of miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome and cost. MAIN RESULTS: There was no evidence of a difference in live birth or clinical pregnancy rate between LOD and gonadotrophins and the pooled odds ratios (OR) (all studies) were 1.04 (95% CI 0.59 to 1.85) and 1.08 (95% CI 0.69 to 1.71) respectively. Multiple pregnancy rates were lower with ovarian drilling than with gonadotrophins (1% versus 16%; OR 0.13, 95% CI 0.03 to 0.52). There was no evidence of a difference in miscarriage rates between the two groups (OR 0.81, 95% 0.36 to 1.86). AUTHORS' CONCLUSIONS: There was no evidence of a difference in the live birth rate and miscarriage rate in women with clomiphene-resistant PCOS undergoing LOD compared to gonadotrophin treatment. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about long-term effects of LOD on ovarian function.

Surgery versus medical therapy for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) significantly impairs the quality of life of many otherwise healthy women. Perception of HMB is subjective and management usually depends upon what symptoms are acceptable to the individual. Medical treatment options include oral medication and a hormone-releasing intrauterine system (LNG-IUS). Surgical options include conservative surgery (uterine resection or ablation) and hysterectomy. OBJECTIVES: To compare the effectiveness, safety and acceptability of surgery versus medical therapy for HMB. SEARCH STRATEGY: In September 2005 we searched the Cochrane Menstrual Disorders and Subfertility Group trials register Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2005), MEDLINE EMBASE, Current Contents, Biological Abstracts, PsycINFO, and CINAHL. We also searched reference lists of articles retrieved and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: Controlled randomised trials comparing conservative surgery or hysterectomy versus medical therapy (oral or intrauterine) for HMB DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data . MAIN RESULTS: The eight included trials randomised 821 women. In comparisons of oral medication versus surgery, 58% of women randomised to medical treatment had received surgery by two years. Compared to oral medication, endometrial resection was significantly more effective in controlling bleeding (at four months: OR 10.62, 95% CI 5.30 to 21.27) and significantly less likely to cause side effects (at four months: OR 0.15, 95% CI 0.07 to 0.31) and hysterectomy resulted in significantly greater improvements in mental health (at six months p = 0.04). In comparisons of LNG-IUS versus conservative surgery or hysterectomy, at one year there was no statistically significant difference in satisfaction rates or quality of life, though adverse effects were significantly less likely with conservative surgery (OR 0.24, 95% CI 0.11 to 0.49). Two trials found conservative surgery significantly more effective than LNG-IUS in controlling bleeding at one year (OR 3.99, 95% CI 1.53 to 10.38). Two other small trials with longer follow-up found no difference or favoured LNG-IUS - however in both these studies the data were skewed and fewer than two thirds of participants were analysed. Hysterectomy stopped all bleeding but caused serious complications for some women. AUTHORS' CONCLUSIONS: Surgery, especially hysterectomy, reduces menstrual bleeding at one year more than medical treatments but LNG-IUS appears equally effective in improving quality of life. The evidence for longer term comparisons is weak and inconsistent. Oral medication suits a minority of women long term.

Laparoscopic "drilling" by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.

BACKGROUND: Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation (failure to ovulate) are well recognised. Surgical ovarian wedge resection was the first established treatment for anovulatory PCOS patients but was largely abandoned due to the risk of post-surgical adhesions and the introduction of medical ovulation induction with clomiphene and gonadotrophins. However patients with PCOS treated with gonadotrophins often have an over-production of follicles and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Moreover ovulation induction with gonadotrophins, though effective, is an expensive, inconvenient and time-consuming treatment requiring intensive monitoring. Surgical therapy with laparoscopic ovarian "drilling" (LOD) may avoid or reduce the need for gonadotrophins or may facilitate their use. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception, and/or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. SEARCH STRATEGY: We used the search strategy of the Menstrual Disorders and Subfertility Group. SELECTION CRITERIA: We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS that undertook laparoscopic ovarian drilling in order to induce ovulation. DATA COLLECTION AND ANALYSIS: Fifteen trials were identified and six were included in the review. All trials were assessed for quality criteria. The primary outcomes were live birth, ovulation and pregnancy rates and the secondary outcomes were rates of miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome and cost. MAIN RESULTS: There was no evidence of a difference in live births or ongoing pregnancies between LOD and gonadotrophins and the pooled Odds Ratio (OR) (all studies) was 1.04 (95% CI 0.74, 1.99) and 1.16 (95% CI 0.72, 1.86) respectively. Multiple pregnancy rates were lower with ovarian drilling than with gonadotrophins (1% vs 16%, OR: 0.13, 95% CI: 0.03 to 0.59). There was no evidence of a difference in miscarriage rates between the two groups (OR 0.81, 955% 0.36, 1.86). AUTHORS' CONCLUSIONS: There was no evidence of a difference in the live birth rate and miscarriage rate in women with clomiphene resistant PCOS undergoing LOD compared to gonadotrophin treatment. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about long term effects of LOD on ovarian function.

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.

BACKGROUND: Overall survival rates are disappointing for women with early poor prognosis breast cancer. Autologous transplantation of bone marrow or peripheral stem cells (in which the patient is both donor and recipient) has been considered a promising technique because it allows much higher doses of chemotherapy to be used. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. Outcomes were survival rates, toxicity and quality of life. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group specialised register, The Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), PsycINFO (1984 to November 2004), Cinahl (1982 to November 2004), web sites of co-operative research groups and ASCO (American Society of Clinical Oncologists) and reference lists of articles found. SELECTION CRITERIA: Randomised controlled trials comparing high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. DATA COLLECTION AND ANALYSIS: Fifteen trials were considered. Thirteen were included and two were excluded. Three independent reviewers extracted data. MAIN RESULTS: Analysis included 2535 women randomised to receive high dose chemotherapy with autograft and 2529 randomised to receive conventional chemotherapy. There were 65 treatment-related deaths on the high dose arm and four on the conventional dose arm (RR 8.58 (95% CI 4.13, 17.80). Many studies have not completed follow-up and have reported only preliminary results. There was a statistically significant benefit in event-free survival for women in the high dose group at three years (RR 1.12 (95% CI 1.06, 1.19)) and at four years (RR 1.30 (95% CI 1.16, 1.45)). At five and six years there was no statistically significant difference between the groups in event-free survival. With respect to overall survival, there was no statistically significant difference between the groups at any stage of follow up. Morbidity was more common and more severe in the high dose group. However there was no statistically significant difference between the groups with respect to the incidence of second cancers at five to seven years' follow up. Women in the high dose group reported significantly worse quality of life scores immediately after treatment, but few statistically significant differences were found between the groups by one year. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of high dose chemotherapy with autograft for women with early poor prognosis breast cancer.

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer.

BACKGROUND: There is a hypothesis that high dose chemotherapy with autologous bone marrow or peripheral stem cell transplantation (autograft) may improve survival for women with metastatic breast cancer. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autologous bone marrow or stem cell transplantation with conventional chemotherapy for women with metastatic breast cancer. SEARCH STRATEGY: We used the Cochrane Breast Cancer Group search strategy, adding these terms: bone marrow transplantation, stem cell transplantation, autologous stem cell support. The following databases were searched: MEDLINE (until November 2004), EMBASE (until November 2004), ASCO (American Society of Clinical Oncology) (1995-2004) and the COCHRANE LIBRARY (Issue 4 2004). We searched the Cochrane Breast Cancer Group database and cooperative research groups' websites for unpublished trials. SELECTION CRITERIA: Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft with conventional chemotherapy for women with metastatic breast cancer. Studies included one or more of the following outcomes: treatment related mortality, overall or progression-free survival at 1, 2, 3, 5 or 7 years, morbidity, quality of life measures, time to tumour progression, overall survival time. DATA COLLECTION AND ANALYSIS: Six randomised controlled trials met the inclusion criteria. Two independent reviewers extracted data. MAIN RESULTS: In total 438 eligible women were randomised to receive high dose chemotherapy with autograft and 412 were randomised to receive conventional treatment. There were fifteen treatment-related deaths among the high dose group and two in the control (conventional dose) group (RR 4.07 (95% CI 1.39, 11.88)). There was no statistically significant difference in overall survival between the high dose and control groups at one year, three years or five years. At one and five years of follow up, there was a statistically significant difference in event-free survival, favouring the high dose group (one year: RR 1.76 (95% CI 1.40, 2.21); five years: RR 2.84 (95% CI 1.07, 7.50). Toxicity was more severe in the high dose group. Only one of the trials has followed up all women for five years and further data are awaited. AUTHORS' CONCLUSIONS: Although there is statistically significant evidence that high dose chemotherapy and autograft improves event free survival compared to conventional chemotherapy, there is no statistically significant evidence of benefit in overall survival for women with metastatic breast cancer. High dose chemotherapy with bone marrow or stem cell transplantation should not be given to women with metastatic breast cancer outside of clinical trials.

Long term hormone therapy for perimenopausal and postmenopausal women.

BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms. It has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women but the evidence supporting its use for these indications is largely observational. OBJECTIVES: To assess the effect of long-term HT on mortality, heart disease, venous thromboembolism, stroke, transient ischaemic attacks, breast cancer, colorectal cancer, ovarian cancer, endometrial cancer, gallbladder disease, cognitive function, dementia, fractures and quality of life. SEARCH STRATEGY: We searched the following databases up to November 2004: the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biological Abstracts. Relevant non-indexed journals and conference abstracts were also searched. SELECTION CRITERIA: Randomised double-blind trials of HT (oestrogens with or without progestogens) versus placebo, taken for at least one year by perimenopausal or postmenopausal women. DATA COLLECTION AND ANALYSIS: Fifteen RCTs were included. Trials were assessed for quality and two review authors extracted data independently. They calculated risk ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Clinical heterogeneity precluded meta-analysis for most outcomes. MAIN RESULTS: All the statistically significant results were derived from the two biggest trials. In relatively healthy women, combined continuous HT significantly increased the risk of venous thromboembolism or coronary event (after one year's use), stroke (after 3 years), breast cancer (after 5 years) and gallbladder disease. Long-term oestrogen-only HT also significantly increased the risk of stroke and gallbladder disease. Overall, the only statistically significant benefits of HT were a decreased incidence of fractures and colon cancer with long-term use. Among relatively healthy women over 65 years taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thromboembolism. No trials focussed specifically on younger women. However, one trial analysed subgroups of 2839 relatively healthy 50 to 59 year-old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT; their absolute risk remained very low. AUTHORS' CONCLUSIONS: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women.

Nonsteroidal anti-inflammatory drugs for primary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea is a common gynaecological complaint consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea. Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs which act by blocking prostaglandin production. OBJECTIVES: The purpose of this review is to compare all nonsteroidal anti-inflammatory drugs used in the treatment of primary dysmenorrhoea with placebo, with paracetamol and with each other to evaluate their effectiveness and safety. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (11 April 2003), Cochrane Central Register of Controlled Trials (1st quarter 2003), MEDLINE (1966-April 2003), and EMBASE (1980 - Week 15 2003). Attempts were also made to identify trials from the National Research Register and the Clinical Trials Register. Citation lists of relevant publications, review articles, abstracts of major scientific meetings and included studies were also searched. SELECTION CRITERIA: All randomised controlled comparisons of NSAID therapies versus placebo, versus other NSAIDs or versus paracetamol when used to treat primary dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Crossover trial data were presented in additional tables and other data were summarised descriptively. MAIN RESULTS: In women with dysmenorrhoea, NSAIDs were found significantly more effective for pain relief than placebo (OR 7.91, 95% CI 5.65 to 11.09), though overall adverse effects were also significantly more common (OR 1.52 95% CI 1.09 to 2.12). When NSAIDs were compared with each other or with paracetamol, there was little evidence of the superiority of any individual NSAID with regard to either efficacy or safety. However the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials, most of which were unsuitable for meta-analysis. REVIEWER'S CONCLUSIONS: NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the most safe and effective for the treatment of dysmenorrhoea.

Surgery versus medical therapy for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding significantly impairs the quality of life of many otherwise healthy women. Perception of heavy bleeding is highly subjective and management of the condition usually depends upon the degree of bleeding and discomfort found acceptable by the individual woman. Medical treatment options include oral medications and a hormone-releasing intrauterine system (LNG-IUS). Surgical options include conservative surgery (uterine resection or ablation) and hysterectomy. OBJECTIVES: To compare the effectiveness, safety and acceptability of surgery versus medical therapy for heavy menstrual bleeding. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (October 2002), Cochrane Controlled Trials Register (Issue 3, 2002), MEDLINE (1966 to October 2002), EMBASE (1980 to October 2002), Current Contents (1993 to week 45, 2002), Biological Abstracts (1969 to September 2002), PsycINFO (1985 to October 2002), CINAHL (1982 to October 2002), and reference lists of articles. We also contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: Controlled randomised trials comparing surgery (conservative surgery and hysterectomy) versus medical therapy (both oral and intrauterine) for heavy menstrual bleeding DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. MAIN RESULTS: Five trials met the inclusion criteria. They randomised 625 women, 311 to receive surgery and 314 to receive medical treatment. One trial compared endometrial resection with oral medication: surgery proved significantly more effective in controlling bleeding (OR 10.62, 95% CI 5.30 to 21.27) and significantly less likely to cause side effects (OR 0.15, 95% CI 0.07 to 0.31). In the other four trials the medical arms received LNG-IUS and the surgical arms received conservative surgery or hysterectomy. At one year no statistically significant difference was shown between LNG-IUS and any surgical treatment in satisfaction rates or quality of life, though conservative surgery was significantly less likely to cause adverse effects (OR 0.24, 95% CI 0.11 to 0.49). Although conservative surgery was significantly more effective than LNG-IUS in controlling bleeding at one year (OR 3.99, 95% CI 1.53 to 10.38), a small trial showed no significant difference between the treatments at two and three years. Hysterectomy stopped all bleeding but caused serious complications for some women. REVIEWER'S CONCLUSIONS: Surgery reduces menstrual bleeding at one year more than medical treatments, but LNG-IUS appears equally beneficial in improving quality of life and may control bleeding as effectively as conservative surgery over the long term. Oral medication suits a minority of women long term.

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.

BACKGROUND: Overall survival rates are disappointing for women with early poor prognosis breast cancer. There is a hypothesis that high dose chemotherapy with autologous bone marrow or stem cell transplant (autograft) may improve survival rates by permitting higher doses of adjuvant chemotherapy to be given. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group specialised register, The Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2002), MEDLINE (1966 to Aug. 2002), EMBASE (1980 to Aug. 2002), PsycINFO (1984 to Aug. 2002), Cinahl (1982 to July 2002), the websites of co-operative research groups and ASCO (American Society of Clinical Oncologists) and reference lists of articles found. SELECTION CRITERIA: Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. DATA COLLECTION AND ANALYSIS: We identified nine trials that met the inclusion criteria. Three independent reviewers extracted data. MAIN RESULTS: In total 1758 women were randomised to receive high dose chemotherapy with autograft and 1767 women were randomised to receive conventional chemotherapy. There were 48 non cancer-related deaths on the high dose arm and four on the conventional dose arm (RR 7.74, 95% CI (3.43, 17.50). Since many studies have not completed follow-up, overall survival rates were in most cases based on results to date. There was no statistically significant difference in overall survival between women who received high dose chemotherapy with autograft and women who received conventional chemotherapy, either at three years (RR 1.02, 95% CI (0.98, 1.06)), or at five years (RR 0.98, 95% CI (0.93, 1.05)). There was a statistically significant benefit in event-free survival at three years for the group who received high dose chemotherapy (RR 1.11, 95% CI (1.05, 1.18)). However at five years there was no statistically significant difference between the groups (RR 1.00, 95% CI (0.92, 1.08)). Side-effects were more common and more severe in the high dose group though most were reversible. Women in the high dose group reported significantly worse quality of life scores immediately after treatment but at one year there was no statistically significant difference between the groups in quality of life scores. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the routine use of high dose chemotherapy with autograft for women with early poor prognosis breast cancer.

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer.

BACKGROUND: There is a hypothesis that high dose chemotherapy with autologous bone marrow or stem cell transplantation (autograft) may improve survival for women with metastatic breast cancer. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autologous bone marrow or stem cell transplantation with conventional chemotherapy for women with metastatic breast cancer. SEARCH STRATEGY: We used the Cochrane Breast Cancer Group search strategy, adding these terms: bone marrow transplantation, stem cell transplantation, autologous stem cell support. The following databases were searched: MEDLINE (until August 2002), EMBASE (until July 2002), ASCO (American Society of Clinical Oncology) (1995-2002) and the COCHRANE LIBRARY (Issue 3 2002). We searched the Cochrane Breast Cancer Group database and cooperative research groups' websites for unpublished trials. SELECTION CRITERIA: Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft with conventional chemotherapy for women with metastatic breast cancer. Studies included one or more of the following outcomes: treatment related mortality, overall or progression-free survival at 1, 2, 3, 5 or 7 years, morbidity, quality of life measures, time to tumour progression, overall survival time. DATA COLLECTION AND ANALYSIS: Five randomised controlled trials met the inclusion criteria. Two independent reviewers extracted data. MAIN RESULTS: In total 382 women were randomised to receive high dose chemotherapy with autograft and 358 were randomised to receive conventional treatment. There were ten treatment related deaths among the high dose group and none reported in the control (conventional dose) group (RR 5.70, 95%CI (1.30, 25)). There was no statistically significant difference in overall survival between the high dose and control groups (at one year: RR 0.99, 95% CI (0.91, 1.08); three years: RR 1.16 95% CI (0.90, 1.51); five years: RR 1.28, 95% CI (0.72, 2.27)). At one and two years of follow up, a statistically significant difference in progression free survival was reported, favouring the high dose group (one year: RR 1.81, 95% CI (1.39,2.34); two years: RR 1.96, 95% CI (1.32, 2.90 ). However this difference was not evident at three or five years (three years: RR 1.44, 95% CI (0.85, 2.44); five years: RR 1.21, 95% CI (0.40, 3.69). Toxicity was more severe in the high dose group. None of the trials has completed follow up and further data are awaited. REVIEWER'S CONCLUSIONS: Although there is evidence that high dose chemotherapy and autograft improves progression free survival at one and two years' follow up compared to conventional chemotherapy, there is no evidence of benefit in overall survival.

A screening test of auditory comprehension for individuals with severe physical disability (PACST).

Tests of auditory comprehension are frequently unsuitable for patients with physically disabling conditions as they require abilities such as good vision or physical manipulation of test materials. A suitable test is required to assess patients who can only indicate 'yes' or 'no'. This has implications for enabling patients to make decisions about their care. A test consisting of 60 Yes-No questions was developed from a larger set tested on normals. A clinical trial was completed and the test found to be a useful tool. It allocates patients to three groups: normal, impaired and chance performance.

Assessing auditory comprehension in the context of severe physical disability: the PACST.

Existing tests of auditory comprehension are frequently unsuitable for patients with physically disabling conditions as tests require skills such as physical manipulation of materials. A suitable test is required to assess the reliability and validity of responses in patients who can only indicate 'yes' and 'no'. This has implications for enabling patients to participate, for example, in decision making over their care. In the construction of the Putney Auditory Comprehension Screening Test (PACST) 200 normal participants were tested with 258 yes/no questions. From their results a test consisting of 60 unambiguous questions, varying in difficulty, type, syntactic complexity and length were selected. A clinical trial was completed with 112 patients from the Royal Hospital for Neuro-disability. The 60 item test was found to be reliable and valid. Results were also compared with independent ratings by ward managers and speech and language therapists. Effects of demographic variables were as expected. A 60 question test was developed which was shown by the clinical trial to be a useful tool. Questions vary in difficulty, but not enough to establish a difficulty gradient. On the basis of performance on the test, patients can be allocated to three groups: normal, impaired, and chance performance.