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R Lilford

Publications and source records attributed to R Lilford.

At least 19 recordsLinked to original sources

Effects of redesigned community postnatal care on womens' health 4 months after birth: a cluster randomised controlled trial.

BACKGROUND: Much postpartum physical and psychological morbidity is not addressed by present care, which tends to focus on routine examinations. We undertook a cluster randomised controlled trial to assess community postnatal care that has been redesigned to identify and manage individual needs. METHODS: We randomly allocated 36 general practice clusters from the West Midlands health region of the UK to intervention (n=17) or control (19) care. Midwives from the practices recruited women and provided care. 1087 (53%) of 2064 women were in practices randomly assigned to the intervention group, with 977 (47%) women in practices assigned to the control group. Care was led by midwives, with no routine contact with general practitioners, and was extended to 3 months. Midwives used symptom checklists and the Edinburgh postnatal depression scale (EPDS) to identify health needs and guidelines for the management of these needs. Primary outcomes at 4 months were obtained by postal questionnaire and included the women's short form 36 physical (PCS) and mental (MCS) component summary scores and the EPDS. Secondary outcomes were women's views about care. Multilevel analysis accounted for possible cluster effects. FINDINGS: 801 (77%) of 1087 women in the intervention group and 702 (76%) of 977 controls responded at 4 months. Women's mental health measures were significantly better in the intervention group (MCS, 3.03 [95% CI 1.53-4.52]; EPDS -1.92 [-2.55 to -1.29]; EPDS 13+ odds ratio 0.57 [0.43-0.76]) than in controls, but the physical health score did not differ. INTERPRETATION: Redesign of care so that it is midwife-led, flexible, and tailored to needs, could help to improve women's mental health and reduce probable depression at 4 months' postpartum.

Adult↗

Tubal flushing for subfertility.

BACKGROUND: A possible therapeutic effect of diagnostic tubal patency testing has been debated in the literature for half a century. Further debate surrounds whether oil-soluble or water-soluble contrast media might have the bigger fertility-enhancing effect. Historically a variety of agents have been used to 'flush' the fallopian tubes, although tubal flushing does not currently form part of routine practice in the treatment of fertility delay. OBJECTIVES: To evaluate the effect of flushing a woman's fallopian tubes with oil- or water-soluble contrast media on subsequent pregnancy outcomes in couples with infertility. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group and a recent search of electronic databases completed in December 2001 was used for the identification of relevant randomised controlled trials. SELECTION CRITERIA: All randomised trials where tubal flushing with oil-soluble contrast media or tubal flushing with water-soluble media was compared with one another or with no treatment were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Eight randomised controlled trials were identified and included in this review. A further one randomised controlled trial is ongoing. All trials were assessed for quality criteria. The studied outcomes were pregnancy, live birth (and ongoing pregnancy), miscarriage, ectopic pregnancy, treatment complications including pain, intravasation of contrast medium, infection and haemorrhage, and image quality. MAIN RESULTS: Tubal flushing with oil-soluble media versus no intervention was associated with a significant increase in the odds of pregnancy (OR 3.57, 95%CI 1.76-7.23). There were no data from RCTs to assess tubal flushing with water-soluble media versus no intervention. Tubal flushing with oil-soluble media was associated with a significant increase in the odds of live birth versus tubal flushing with water-soluble media (OR 1.49, 95%CI 1.05-2.11) but the odds of pregnancy showed no significant difference (OR 1.23, 95%CI 0.95-1.60) and there was evidence of statistical heterogeneity for these two outcomes. The addition of oil-soluble media to flushing with water-soluble media (water-soluble plus oil-soluble media versus water-soluble media alone) showed no significant difference in the odds of pregnancy (OR 1.16, 95%CI 0.78-1.70) or live birth (OR 1.06, 95%CI 0.64-1.77). REVIEWER'S CONCLUSIONS: There is some evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy versus no intervention. The limited evidence of an increase in the odds of live birth from tubal flushing with oil-soluble contrast media versus water-soluble contrast media must be interpreted cautiously. Further robust randomised trials, comparing oil-soluble versus water-soluble media and comparing each versus no intervention, are required to provide convincing evidence as to whether the technique should be accepted into widespread clinical practice.

Contrast Media↗

Underpowered studies.

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Clinical Trials as Topic↗

How can action research apply to health services?

The authors ask whether and how action research can apply to health services research, given action research's claim to be radically different from mainstream research. They analyze the key tenets of an idealized version of action research, comparing them with those of the approach characteristic of mainstream research. The authors conclude, firstly, that action research deserves all credit for pioneering flexible and imaginative ways of working. Yet, there is nothing in the fundamental logic of the mainstream approach to preclude it from adopting some of these. Action researchers therefore need to reconsider their critical stance toward mainstream research. Conversely, mainstream researchers need to reconsider their critical stance toward the ways of working pioneered by action research and to adopt them as appropriate.

Delivery of Health Care↗

Oil-soluble versus water-soluble media for assessing tubal patency with hysterosalpingography or laparoscopy in subfertile women.

BACKGROUND: There has been debate in the literature for more than 40 years as to whether flushing of the Fallopian tubes enhances fertility and whether this presumed therapeutic effect is greater with oil-soluble media than with water-soluble media. A meta-analysis of the therapeutic role of oil-soluble contrast media at hysterosalpingography was published in March 1994 (Watson 1994). This Cochrane Review is an expansion and update of that overview. OBJECTIVES: To evaluate the effect of flushing the Fallopian tubes with oil- or water-soluble contrast media on subsequent pregnancy rates in infertility patients. SEARCH STRATEGY: 1. For randomised controlled trials (RCTs): we searched the Cochrane Subfertility Review Group specialised register of controlled trials. 2. For non-randomised controlled studies: Medline and manual search of eight relevant journals. SELECTION CRITERIA: Six RCTs and six non-randomised controlled studies. In two studies tubal flushing was compared with no treatment-controls. Eleven studies, comprising a total of 2635 subjects, compared oil- with water-soluble media. DATA COLLECTION AND ANALYSIS: Independently by first 2 authors for: 1. Methodological trial characteristics 2. Characteristics of participants 3. OUTCOMES: the main studied outcome was pregnancy rate per patient MAIN RESULTS: In comparison with no treatment, a significant benefit on pregnancy rates was seen by flushing the tubes with oil-soluble media (OR 1.80, 95% CI 1.29-2.50) but not with water-soluble media (OR 0.87, 95% CI 0.50-1.52). In the direct comparison of oil- and water-soluble media the former lead to significantly higher pregnancy rates (OR 1.92, 95% CI 1.60-2.29). The treatment effect appeared similar in RCTs and non-RCTs. Subgroup analysis suggested the therapeutic benefit was greatest for patients suffering from unexplained infertility and least for those with tubal factor infertility. REVIEWER'S CONCLUSIONS: Flushing of the tubes with oil-soluble media increases subsequent pregnancy rates in infertility patients. The hypothesis that tubal "plugs" are a cause of proximal tubal occlusion and that oil-soluble media may flush them out, is supported by new techniques such as falloposcopy. Clinicians should consider flushing the tubes with OSCM before contemplating more invasive therapies.

Contrast Media↗

Androgens versus placebo or no treatment for idiopathic oligo/asthenospermia.

BACKGROUND: Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility. Androgens have been suggested as a treatment because its binding proteins maintain a maintain a high intratesticular level testosterone essential for spermatogenesis and because the epididymis and seminal vesicles affect the seminal constitution and sperm motility and are also androgen-dependent. However exogenous testosterone was found to exert negative feedback on the pituitary-gonadal axis and thereby to suppress FSH and LH secretion. Spermatogenesis was thus adversely affected. Nevertheless androgens are used for the treatment of male infertility either for a putative direct "stimulatory" or "rebound" therapy. The stimulatory androgens used are mesterolone and testosterone undecanoate which, it is postulated, in a form and dosage that does not influence pituitary gonadotrophin secretion, either have a direct stimulatory effect on spermatogenesis or influence sperm transport and maturation though an effect on the epididymis, ductus deferens and seminal vesicles. Other androgens have been used to produce a rebound effect. These androgens are administered to suppress gonadotrophin secretion and spermatogenesis. After androgen therapy is discontinued there is a surge of FSH and LH and spermatogenesis is recommenced. Because of their different proposed mechanisms of action, stimulatory and rebound androgen therapy are analysed separately in the comparisons. This review considers the available evidence of the effect of androgens for idiopathic oligo and/or asthenospermia. OBJECTIVES: The objective of this review was to assess the effect of androgen treatment of men among couples where failure to conceive has been attributed to idiopathic oligo- and/or asthenospermia. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of mesterolone or testosterone undecanoate versus placebo or no treatment (stimulatory therapy), or testosterone enanthate or testosterone undecanoate versus placebo or no treatment (rebound therapy) in couples where subfertility is attributed to male factor. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. MAIN RESULTS: Eleven trials involving 930 patients were included. For stimulatory therapy, androgens had little effect on endocrinal outcomes and sperm parameters. The rate of pregnancy after androgens with stimulatory effect compared to no treatment or placebo was also similar (odds ratio 1.10, 95% confidence interval 0.75 to 1.61). In rebound therapy, no difference was found in sperm parameters. The pregnancy rate after androgens with rebound effect also showed no difference compared to no treatment or placebo (odds ratio 1.60, 95% confidence interval 0.42 to 6.16). Adverse effects such as headaches and exanthema were reported. REVIEWER'S CONCLUSIONS: There is not enough evidence to evaluate the use of androgens for male subfertility. [This abstract has been prepared centrally.]

Androgens↗

Clomiphene or tamoxifen for idiopathic oligo/asthenospermia.

BACKGROUND: Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility. The administration of anti-oestrogens is a common treatment because anti oestrogens interfere with the normal negative feedback of sex steroids at hypothalamic and pituitary levels in order to increase endogenous gonadotropin-releasing hormone secretion from the hypothalamus and FSH and LH secretion directly from the pituitary. In turn, FSH and LH stimulate Leydig cells in the testes, and this has been claimed to lead to increased local testosterone production, thereby boosting spermatogenesis with a possible improvement in fertility. There may also be a direct effect of anti-oestrogens on testicular spermatogenesis or steroidogenesis. This review considers the available evidence of the effect of both Clomiphene citrate and tamoxifen, both of which have a predominant anti-oestrogenic effect, for idiopathic oligo and/or asthenospermia. OBJECTIVES: The objective was to assess the effects of treating subfertile men with anti-oestrogens (clomiphene or tamoxifen) on pregnancy rates among couples where subfertility has been attributed to idiopathic oligo- and/or asthenospermia. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of anti-oestrogen therapy for 3 months or more compared to placebo or no placebo for subfertile males among couples where subfertility is attributed to male factor. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Any differences were resolved with a third reviewer. MAIN RESULTS: Ten studies involving 738 men were included. Five of the trials did not specify method of randomisation. Anti-oestrogens had a positive effect on endocrinal outcomes, such as serum testosterone levels. In trials with secure randomisation there was no difference in the pregnancy rate between the anti-oestrogen groups and the control groups (odds ratio 1.26, 95% confidence interval 0.99 to 1.56). The overall pregnancy rate for these five trials was 15.4% compared to the spontaneous rate of 12.5% in the control groups. These odds increased to 1.56 (95% confidence interval 0.99 to 2.19) when all 10 trials were included, but this result is likely to be artificially inflated. REVIEWER'S CONCLUSIONS: Anti-oestrogens appear to have a beneficial effect on endocrinal outcomes, but there is not enough evidence to evaluate the use of anti-oestrogens for increasing the fertility of males with idiopathic oligo-asthenospermia.

Clomiphene↗

Bromocriptine for idiopathic oligo/asthenospermia.

BACKGROUND: Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology)of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility. Whilst bromocriptine treatment for reducing prolactin levels in hyperprolactinaemic males (as in females), and, in the treatment of hypogonadotropic hypogonadism with hyperprolactinaemia, is beneficial, it has also been used for oligospermic men in the absence of any endocrinopathy. Prolactin may play a direct role in spermatogenesis and hormone production. It has also been claimed that in oligospermic men with normal gonadotrophins mean prolactin levels are higher and that hyperprolactinaemia is more common compared to fertile men. It has been proposed that the administration of bromocriptine under these circumstances might counteract a prolactin-induced block on the action of gonadotrophins on the testicles and, subsequently, that the reduction in prolactin levels might lead to an improvement in semen parameters and fertility. Although it is not licensed for use in male infertility, bromocriptine has been used for normogonadotrophic individuals with oligospermia and normal or sligthly elevated prolactin levels. This review considers the available evidence of the effect of bromocriptine therapy for normoprolactinaemic males with idiopathic oligo and/or asthenospermia. OBJECTIVES: The objective of this review was to assess the effects of bromocriptine on pregnancy rates among couples where subfertility has been attributed to idiopathic oligo- and/or asthenospermia. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: Randomised trials of oral bromocriptine versus placebo or no treatment for couples with subfertility attributed to male factor. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and any disagreements were resolved by discussion with other reviewers. MAIN RESULTS: Four studies were included. The method of randomisation was not specified in any of the trials, which were all of crossover design. Compared with placebo, bromocriptine was associated with a significant reduction in serum prolactin levels (weighted mean difference -195.3 micro international units per litre, 95% confidence interval -276.5 to -114). No effects on sperm parameters were seen. There was also no effect on pregnancy rates observed between bromocriptine and placebo (0.70 odds ratio, 95% confidence interval 0.15 to 3.24). REVIEWER'S CONCLUSIONS: Bromocriptine appears to reduce prolactin levels in subfertile men with normal gonadotrophic function. There is not enough evidence to show that bromocriptine is helpful in improving fertility.

Bromocriptine↗

Kinin-enhancing drugs for unexplained subfertility in men.

BACKGROUND: Oligo-astheno-teratospermia (sperm of low concentration, reduced motility and increased abnormal morphology) of unknown cause is common and the need for treatment is felt by patients and doctors alike. As a result, a variety of empirical, non-specific treatments have been used in an attempt to improve semen characteristics and fertility. One suggested treatment for idiopathic oligo- and/or asthenospermia is the administration of kallikrein (kallidinogenase), a kinin-releasing enzyme (or kininogenase). The kinin biological system is complex and involves kininogen (the substrate), kininogenases (the activating enzymes), kinins (the effectors) and kininases (the inactivating enzymes). All four components of the kinin system have been found in the genitalia and in semen. Kallikrein releases 2 major kinins, kallidin and bradykinin, from seminal plasma kininogens. Activated kinins in semen affect sperm motility and metabolism. In vitro addition of kallikrein to semen has been shown to have a positive effect on sperm motility, sperm velocity, cervical mucus penetration, penetration of zona-free hamster eggs and post-thaw survival and motility rate after semen cryopreservation. The latter observation, however, was not confirmed in a more recent comparison of motility stimulants for cryopreserved semen using computerised sperm motion analysis. In vitro treatment of semen with kallikrein has been employed in a clinical context during sperm preparation prior to insemination. Although the kinin system may also be involved in the regulation of spermatogenesis in vivo, a clear mechanism of action is missing. Multiple suggestions on how an increase in kinin levels in the genital tract influences spermatogenesis at the testicular levels have been made by various authors. OBJECTIVES: To determine whether treatment of the male with drugs enhancing kinin levles increases pregnancy rates among couples where failure to conceive has been attributed to idiopathic oligo- and/or asthenospermia. Effects on sperm parameters and sex hormones were studied as secondary outcomes. SEARCH STRATEGY: The Cochrane Subfertility Review Group specialised register of controlled trials was searched". SELECTION CRITERIA: SIxteen RCTs on the therapeutic use of androgens (clomiphene citrate or tamoxifen) in subfertile men were identified. Six trials were excluded. DATA COLLECTION AND ANALYSIS: Methodological characteristics of trials Baseline characteristics of the studied groups Outcomes: Pregnancy rates, semen parameters (sperm concentration, motility and morphology), endocrinology (serum FSH, testosterone and oestradiol)

Fertility Agents, Male↗

Techniques for pelvic surgery in subfertility.

BACKGROUND: Since the advent of in-vitro fertilisation (IVF) the role of infertility surgery has diminished. This type of surgery is still however widely performed.and there are many different surgical techniques that can be used to repair blocked or damaged Fallopian tubes. Most evidence in this area comes from uncontrolled series. OBJECTIVES: To evaluate surgical techniques for the treatment of tubal infertility (adhesiolysis, salpingostomy, surgery for proximal tubal occlusion, reversal of sterilisation). SEARCH STRATEGY: This review has drawn on the search strategy developed for the Subfertility Group as a whole. Relevant trials were identified from the Group's Register of Controlled Trials. SELECTION CRITERIA: All randomised controlled trials investigating an aspect of infertility surgery technique. Non-randomised data were included for the following topics 1) The role of infertility surgery versus no treatment 2) The role of infertility surgery versus alternative treatments, 3) the role of magnification, 4) The role of the CO2 laser at infertility surgery, 5) the role of operative laparoscopy to perform infertility surgery. Non- RCT data were excluded if :- i) The treatment and control groups differed significantly ii) The treatment and control groups were operated by a different team or in a different institute iii) Where pregnancy outcome data were not given. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the first 2 authors. Differences of opinion were registered and resolved by consensus with the senior author (RL). Two by two tables were generated for each trial for the dichotomous outcome of pregnancy and the effects on pregnancy rate of each study is expressed as an odds ratio with 95% confidence intervals. MAIN RESULTS: 1) INFERTILITY SURGERY VERSUS NO TREATMENT One non RCT compared open adhesiolysis versus no treatment and found significantly more pregnancies in the treatment group compared with the control group. 2) INFERTILITY SURGERY VERSUS ALTERNATIVE TREATMENTS. No RCTs investigated the role of infertility surgery compared with In vitro fertilisation (IVF). There were no studies comparing tubal surgery for proximal tubal occlusion versus hysteroscopic or radiologically controlled recannulation. 3) MAGNIFICATION FOR INFERTILITY SURGERY There was a non significant reduction in pregnancy rate when the operating microscope (magnification x4-x16) was used rather than Loupes (magnification x2-x4.5) in the only RCT to study this. One RCT randomised patients to microsurgery versus a macrosurgical technique involving a prosthesis. There were more pregnancies in the microsurgery group, but this was not significant, and the trial consisted of only 18 participants. All the non-RCT studies comparing microsurgery with macrosurgery had a historical control group. Meta-analysis of studies investigating the role of magnification for adhesiolysis and for salpingostomy revealed a statistically significant increase in pregnancy rates and reduction in ectopic pregnancy rates for microsurgery versus macrosurgery for both procedures. For reversal of sterilisation there was a significant improvement in term pregnancy rates, and a non significant reduction in ectopic rates There was no significant difference between microsurgical and macrosurgical treatment of proximal tubal occlusion for any outcome. 4) THE USE OF LASER AT INFERTILITY SURGERY Two RCTs investigated the use of the CO2 laser at infertility surgery. There was no significant difference in pregnancy outcome after adhesiolysis, or salpingostomy. Two non randomised studies also investigated the role of the laser. Overall there was no significant difference using the CO2 laser compared with standard techniques for adhesiolysis, salpingostomy or reversal of sterilisation. 5) LAPAROSCOPIC INFERTILITY SURGERY Four studies investigated the use of laparoscopic techniques for infertility surgery. There were no RCTs. One study compared laparoscopic versus open

Fallopian Tube Diseases↗

Gonadotrophin therapy for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: Approximately 15% of patients with PCOS remain anovulatory despite treatment with oral anti-oestrogen medications such as clomiphene citrate. In addition, about half of women with PCOS ovulating on anti-oestrogen treatment fail to conceive. Gonadotrophin stimulation is the next step in treatment for women who are "clomiphene resistant", however, results of gonadotrophin stimulation in women with PCOS are less successful. In PCOS associated with hypersecretion of LH, purified urinary follicle-stimulating hormone (u-FSH) preparations have theoretical advantages over the use of human menopausal gonadotrophin (hMG) preparations (containing both FSH and LH), but whether this claimed advantage extends into clinical practice remains uncertain. In addition, the use of gonadotrophin-releasing hormone analogues (GnRH-a) to produce pituitary desensitisation prior to ovulation induction in PCOS has been claimed to increase the success rates of treatment as well as reduce complications such as OHSS and multiple pregnancy. Gonadotrophin preparations have also been administered via different routes (intramuscular or subcutaneous), or using different stimulation regimens and protocols (step-up or standard) in an attempt to improve efficacy. OBJECTIVES: To determine the effectiveness of urinary-derived gonadotrophins as ovulation induction agents in patients with PCOS trying to conceive. In particular, to assess the effectiveness of (1) different gonadotrophin preparations, (2) the addition of a gonadotrophin-releasing hormone agonist (GnRH-a) to gonadotrophin stimulation and (3) different modalities of gonadotrophin administration. SEARCH STRATEGY: The search strategy to identify RCTs consisted of (1) the Group's Specialised Register of Controlled Trials using the search strategy developed for the Menstrual Disorders and Subfertility Group as a whole (see the Review Group details for more information), (2) additional specific electronic Medline searches and (3) bibliographies of identified studies and narrative reviews. SELECTION CRITERIA: RCTs in which urinary-derived gonadotrophins were used for ovulation induction in patients with primary or secondary subfertility attributable to PCOS. DATA COLLECTION AND ANALYSIS: Twenty three RCTs were identified, 9 of which were excluded from analysis. The data were extracted independently by 2 authors. The following criteria were assessed: (1) the methodological characteristics of the trials, (2) the baseline characteristics of the studied groups and (3) the outcomes of interest: pregnancy rate (per cycle), ovulation rate (per cycle), miscarriage rate (per pregnancy), multiple pregnancy rate (per pregnancy), overstimulation rate (per cycle) and ovarian hyperstimulation syndrome (OHSS) rate (per cycle). Where suitable, meta-analysis was performed using Peto's OR with 95% CI with the fixed effect Mantel-Haentszel equation. MAIN RESULTS: (1) A reduction in the incidence of OHSS with FSH compared to hMG in stimulation cycles without the concomitant use of a GnRH-a (OR 0.20; 95% CI 0.08-0.46) and (2) a higher overstimulation rate when a GnRH-a is added to gonadotrophins (OR 3.15; 95% CI 1.48-6.70). REVIEWER'S CONCLUSIONS: Although 14 RCTs were included in this review, few dealt with the same comparisons, all were small to moderate size and their methodological quality was generally poor. Any conclusions, therefore, remain tentative as they are based on a limited amount of data and will require further RCTs to substantiate them. In none of the comparisons was there a significant improvement in pregnancy rate but this may be due to the lack of power (i.e. insufficient patients randomised to demonstrate a significant difference between treatments). There was a trend towards better pregnancy rates with the addition of a GnRH-a to gonadotrophin stimulation and these interventions warrant further study. Despite theoretical advantages, urinary-derived FSH preparations did not improve pregnancy rates when compared to traditional and cheaper hMG preparations; their only demonstrable benefit was a reduced risk of OHSS in cycles when administered without the concomitant use of a GnRH-a. No conclusions can be drawn on miscarriage and multiple pregnancy rates due to insufficient reporting of these outcomes in the trials.

Female↗

Pulsatile luteinising hormone releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH) secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase. Treatment with pulsatile GnRH infusion by the intra-venous or subcutaneous route using a portable pump has been used successfully in patients with hypogonadotrophic hypogonadism. Assuming that the results would be similar in polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to induce ovulation in patients with PCOS. But, although ovulation and pregnancy has been achieved, the use of pulsatile GnRH in PCOS patients is controversial. OBJECTIVES: To assess the effectiveness of pulsatile GnRH administration in women with clomiphene-resistant polycystic ovary syndrome (PCOS), in terms of ovulation induction, pregnancy, miscarriage, multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. SELECTION CRITERIA: All relevant published RCTs were selected. Non-randomised controlled trials were eligible for inclusion if treatment consisted of GnRH administration versus another treatment to induce ovulation in subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. One RCT (Bringer 1985a) and one abstract (Coelingh 1983) were identified this way. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed for predetermined quality criteria. DATA SYNTHESIS: 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. MAIN RESULTS: Three RCTs and one non-randomised comparative trial were identified comparing four different treatments: GnRH versus HMG, GnRH following GnRHa pre-treatment versus no pre-treatment, GnRH and FSH versus FSH, and GnRH following GnRHa pre-treatment versus GnRH following oral contraceptive pre-treatment. This means that there was only one trial in any one comparison. In the first two studies, data of pre- and post-cross-over were not described separately. Therefore, these results could not be included in the MetaView analysis. The odds ratio for ovulation rate was 16 (95 % CI: 1.1-239) in the study comparing GnRH and FSH with FSH. When GnRH after GnRHa pre-treatment was compared with GnRH after oral contraceptive pre-treatment, an odds ratio of 7.5 (95 % CI: 1.2-46) was obtained. All trials were small and of too short duration to show any significance in pregnancy results. Per study only one to four pregnancies occurred. Multiple pregnancies were not seen. OHSS was seen only in the patients stimulated with HMG. REVIEWER'S CONCLUSIONS: The four trials describing four different comparisons with a short follow up (1 to 3 cycles) were too small to either prove or discard the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

Female↗

Collection devices for obtaining cervical cytology samples.

OBJECTIVES: The false-negative rate of cervical smears varies between 1.5% and 55%. This variation may be partly due to differences in sampling device and technique. The objective of this review was to assess different cervical sampling devices for collecting endocervical cells, which are thought to be a surrogate for detection of abnormal cells and adequate smear rates. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group trials register and MEDLINE up to July 1997. We also handsearched 16 journals. SELECTION CRITERIA: Randomised and quasi-randomised trials and non-randomised comparative studies comparing cervical smear collection devices in women attending for primary screening, colposcopy following an abnormal smear or colposcopy after treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data. Study quality was assessed. MAIN RESULTS: Thirty-four trials and six observational comparative studies were included. The Ayre spatula was shown to be less effective compared with extended tip spatulas for collecting endocervical cells in eight trials (odds ratio 2.25, 95% confidence interval 2.06 to 2.44). Use of a spatula with the cytobrush was more effective than spatula alone at collecting endocervical cells (odds ratio 3.33, 95% 3.05 to 3.63) and the same effect was present for adequate smear rates (odds ratio 1.51 95% 1.19-1.92). Extended tip spatulas were also superior for the detection of dyskaryosis in seven trials (odds ratio 1.21, 95% confidence interval 1.10 to 1.33). Based on data from two trials and three observational studies, smears that contained endocervical cells were more likely to detect dyskaryosis, particularly in severe disease. The proportion of smears with endocervical cells present increased with increasing severity of the disease. REVIEWER'S CONCLUSIONS: Extended tip spatulas of various designs appear to be better for collecting endocervical cells than the commonly used Ayre spatula. The most effective combination appears to be the cytobrush with an extended tip spatula. The rate of detection of endocervical cells appears to be a valid and convenient surrogate for the ability to detect dyskaryosis and for adequate smear rates. The ability of the extended tip spatula with the cytobrush compared with the extended tip spatula alone to detect disease, needs to be evaluated in a trial.

Female↗

Progestagens for endometrial cancer.

OBJECTIVES: Progestagen therapy following primary surgery for endometrial cancer has been advocated to reduce the risk of recurrence. The objective of this review was to assess the effect of adjuvant progestagen therapy in endometrial cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group trials register and MEDLINE up to May 1999. SELECTION CRITERIA: Randomised trials of progestagen therapy in women who have had surgery for endometrial cancer. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two reviewers abstracted data independently. MAIN RESULTS: Six trials involving 4351 women were identified. Three trials included women with stage one disease only, whereas three included women with more advanced disease. Based on five trials, overall survival was not improved by adjuvant progestagen therapy (OR 1.05, 95% CI 0.88 to 1.24). Endometrial cancer deaths and relapse of disease appears to be reduced by progestagen therapy OR 0.88 95% CI (0.71-1.1) and 0. 81 95% CI (0.65-1.01) respectively. However, non-endometrial cancer related deaths were more common in women treated with progestagens OR 1.33 (1.02-1.73). REVIEWER'S CONCLUSIONS: Current evidence does not support the use of adjuvant progestagen therapy in the primary treatment of endometrial cancer.

17 alpha-Hydroxyprogesterone Caproate↗

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 of the risk of post-surgical adhesion formation. It was replaced by medical ovulation induction with clomiphene and gonadotrophins. However patients with PCOS treated with gonadotrophins often have a polyfollicular response and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Although effective, it is an expensive, stressful and time consuming form of treatment requiring intensive monitoring. A new surgical therapy, laparoscopic ovarian "drilling", may avoid or reduce the need, or facilitate the use, of gonadotrophins for inducing ovulation. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions. It has been claimed in many uncontrolled observational studies that it is followed, at least temporarily, by a high rate of spontaneous postoperative ovulation and conception, or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness of laparoscopic ovarian drilling for ovulation induction in subfertile women with anovulation (failure to ovulate) and polycystic ovarian syndrome (PCOS). SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of randomised controlled trials (RCTS). A computerised MEDLINE search was used to identify non randomised controlled trials. SELECTION CRITERIA: Trials were eligible for inclusion if treatment consisted of laparoscopic ovarian drilling in order to induce ovulation in subfertile women with PCOS and compared with a concurrent control group. DATA COLLECTION AND ANALYSIS: Fourteen trials were identified; eight were included in the review of which seven were randomised. All trials were assessed for quality criteria. The main studied outcomes were ovulation and pregnancy rates. Miscarriage rate, multiple pregnancy rate, and incidence of overstimulation and ovarian hyperstimulation syndrome rate were secondary outcomes. MAIN RESULTS: With the exception of multiple pregnancy rates no differences were demonstrated for any of the interventions studied but the numbers of patients who have been randomised to controlled studies at this time is insufficient to conclude that laparoscopic ovarian drilling is more effective than gonadotrophin therapy for other outcomes. REVIEWER'S CONCLUSIONS: The value of laparoscopic ovarian drilling as a primary treatment for subfertile patients with anovulation (failure to ovulate) and polycystic ovarian syndrome (PCOS) is undetermined. There is insufficient evidence to determine a difference in ovulation or pregnancy rates when compared to gonadotrophin therapy as a secondary treatment for clomiphene resistant women. Multiple pregnancy rates are reduced in those women who conceive following laparoscopic drilling. None of the studied modalities of drilling technique had any obvious advantages.

Anovulation↗

Liquid and fluid agents for preventing adhesions after surgery for subfertility.

BACKGROUND: Pelvic surgery is associated with high rates of both de novo adhesion formation and adhesion reformation. Although the role of pelvic and/or tubal surgery in the management of infertility is more limited since the development of in-vitro fertilisation such surgery remains indicated for a number of selected patients. Other forms of pelvic surgery will remain prevalent in women of reproductive age (e.g. endometriosis surgery, ovarian cystectomy, myomectomy). Since subsequent fertility is reduced with increasing severity of periadnexal adhesions, pelvic adhesions will remain a clinical problem in infertility patients. Adjuvant therapy has been promoted for many years to prevent adhesion formation. Numerous substances have been used experimentally in animal models, many have been advocated for use during human surgery, and some are widely used in clinical practice. Steroids and antihistamines are given in the belief that they will promote fibrinolysis during healing without preventing healing. OBJECTIVES: To investigate whether pharmacological and liquid agents used as adjuvants during pelvic surgery in infertility patients lead to a reduction in the incidence or severity of postoperative adhesion (re-)formation, and/or an improvement in subsequent pregnancy rates. SEARCH STRATEGY: The specialised database of the Menstrual Disorders and Subfertility Group. SELECTION CRITERIA: Randomised controlled trials investigating the use of pharmacological and liquid agents to prevent adhesion formation after pelvic surgery for infertility. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the first 2 authors. Differences of opinion were registered and resolved by consensus with the senior author (RJL). Two by two tables were generated for each trial for the dichotomous outcome of pregnancy and the effects on pregnancy rate of each study is expressed as an odds ratio with 95% confidence intervals. MAIN RESULTS: None of the pharmacological or liquid agents investigated in a randomised controlled fashion was shown to improve postoperative pregnancy rates. There was some evidence that steroids reduced the incidence and severity of postoperative adhesion formation. Dextran appeared to neither reduce the incidence or severity of adhesions. REVIEWER'S CONCLUSIONS: The routine use of pharmacological agents to prevent post-operative adhesions after infertility surgery cannot be recommended on the basis of the available evidence derived from RCTs. In connection with adhesion prevention, the evidence with regard to steroids is far from perfect but tentatively suggests that they may be beneficial. Further randomised studies should be conducted to investigate this further.

Anticoagulants↗

Efficacy of cervical-smear collection devices: a systematic review and meta-analysis.

BACKGROUND: Few randomised controlled trials have sufficient power to show clear advantages of different designs of cervical-smear collection devices. We studied by systematic review whether the design of cervical-smear devices affects rates of inadequate smears and detection of disease and whether the presence of endocervical cells in the smear affects detection of disease. METHODS: We sought relevant randomised controlled trials by computer literature review by MEDLINE backed up by a manual search of 16 journals. Each trial was classified according to methodological quality criteria. Odds ratios were calculated where data allowed. FINDINGS: 34 randomised controlled trials investigating cervical Papanicolaou smear collection devices were identified. All 34 trials compared the ability of devices to collect endocervical cells, and 19 compared the ability of devices to detect dyskaryosis. Meta-analyses showed that compared with other collection devices, the Ayre's spatula is an ineffective device for collecting endocervical cells (for example, odds ratio for comparison of extended-tip spatulas vs Ayre's spatula 2.25 [95% CI 2.06-2.44]) and also gives a lower yield of dyskaryosis (odds ratio for comparison of extended-tip spatulas vs Ayre's spatula 1.21 [1.20-1.33]). Devices that effectively collect endocervical cells also detect a higher proportion of abnormal cytology than those that do not. INTERPRETATION: The widely used Ayre's spatula is the least effective device for cervical sampling and should be superseded by extended-tip spatulas for primary screening and investigation of women before and after treatment for cervical intraepithelial neoplasia. The presence of endocervical cells is a valid and convenient surrogate for the ability to detect dyskaryosis.

Equipment Design↗