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R Lilford

Publications and source records attributed to R Lilford.

At least 37 records · Page 2Linked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

A complex population of RNAs exists in human ejaculate spermatozoa: implications for understanding molecular aspects of spermiogenesis.

The presence of mRNAs in human ejaculate spermatozoa is well established, yet little is known of the representation or function of these transcripts. To address these issues, the complexity of spermatozoal RNA was examined. As expected, testis-expressed mRNAs were detected by RT-PCR in mature human spermatozoa. Interestingly, when a testis cDNA library was probed with total spermatozoal RNA, less than 2% of plaques gave a strong hybridization signal, suggesting a rather unique sperm-derived population. To further define the sequence distribution, 18 strongly hybridizing clones were selected at random for end-sequence analysis. Twelve matched unique sequences in the EST, STS and NR databases, whereas five showed no similarity to any of the sequences in the databases. In addition, one clone belonged to the SINE repetitive element family. As demonstrated by sequencing randomly primed cloned inserts, short (SINE/MER) or long (LINE/ORF2) interspersed repeat-like sequences are also contained as part of the spermatozoal RNA fraction. It is now evident that human spermatozoa contain a rich repertoire of both known and unknown protein-encoding and non-coding RNAs. This provides a unique opportunity to identify and investigate the many genes responsible for the structure and function/dysfunction of the male gamete using spermatozoal RNA as the template.

Amino Acid Sequence↗
PubMed1999

Clinical governance: culture, leadership and power--the key to changing attitudes and behaviours in trusts.

Clinical governance places for legal duty for quality on Trust chief executives. The article deals with how chief executives can overcome the cultural and behavioural obstacles to change which impede the journey to developing effective structures for clinical governance. To establish effective structures for clinical governance, chief executives will need to address these features of organisational life--culture, power and leadership. The article seeks to provide practical ways in which they can do this.

Governing Board↗
PubMed1999

Commissioning health services research: an iterative method.

The standard linear method of commissioning research involves many stages, some lengthy. While assessment criteria are usually explicit, their weighting and interaction are not. Output is assessed on completion. This method is suitable where the research question is clear-cut. However, it has drawbacks when the research question and the form and scope of the research are not clear at the outset, as is often the case with research on the delivery and organisation of services. Also, it does not encourage potential users of the research to develop a sense of ownership. An alternative method is proposed by which the scope, form and content of research are not specified in advance but are developed iteratively. A programme director, advised by a group of potential users and research commissioners, has devolved authority to commit funding for the stages of the work as it unfolds, predicated on evolving need. There are foreseeable but avoidable risks of the group over-identifying with the researchers, of research management becoming cumbersome, and of unproductive friction between research groups when they are required to work together. The iterative method, being new and untried, is itself an organisational change requiring evaluation. However, from our local experience, it provides for productive dialogue between research commissioners, researchers and potential users.

Health Services Research↗
PubMed1998

Decision analysis in the selection, design and application of clinical and health services research.

Research evidence will never be sufficient to tell us how treatments compare in every group or class of patients. It will always be necessary to particularize from the general to the specific. The ad hoc way this is normally done contrasts with the rigour of the research process. However, extrapolating from the general to the particular can be made equally rigorous by Decision Analytic modelling. Furthermore, research evidence is not enough when decisions turn on multiple objectives, which must be traded off against each other. Research evidence and patients' preferences can be reconciled, again rigorously, by using Decision Analysis to show how probabilities and values interact. In addition, research should be designed around likely clinical impact, and this in turn can be made explicit by Decision Analytic modelling. In particular, sample size calculations should be based on such explicit modelling, rather than current procedures, which seldom seek to defend the size of clinical effects sought.

Decision Support Techniques↗
PubMed1997

Short postnatal hospital stay: implications for women and service providers.

BACKGROUND: In a bid to increase consumer satisfaction, recent government reports have encouraged maternity services providers to offer women more choice about their care. At the same time, there has been considerable pressure on hospital managers and clinicians to drive down health service costs. Women need information about the likely effects of different service patterns on their wellbeing, and service providers about the implications of allowing women choice. METHODS: This paper reports on a descriptive study in six districts in the Yorkshire Region and focuses on the implications of variation in length of stay. The aim of the study was to describe variation in the care process and to explore associations between care process variables, consumer satisfaction and maternal psychological wellbeing. One hundred and twenty randomly selected women in each district delivering in a specified four-week period were asked to complete postal survey questionnaires in the postnatal period. RESULTS: There were significant differences between districts in terms of the length of postnatal hospital stay for women experiencing normal deliveries. Those women who thought that their postnatal length of stay was too short had significantly higher depression scores. CONCLUSIONS: Variation in length of postnatal hospital stay may have implications for consumer satisfaction, maternal psychological outcomes and resource use.

Bed Occupancy↗
PubMed1997

Randomised trial comparing a policy of early with selective amniotomy in uncomplicated labour at term.

OBJECTIVE: To compare two management policies: rupture of the fetal membranes when women are in normal labour or leave them intact as long as feasible. SETTING: The labour ward of a city university hospital. DESIGN: Automated randomised clinical trial. PARTICIPANTS: 1540 women in uncomplicated term labour. Data on labour duration, blood loss, oxytocin use and fetal condition were collected from 1132 women. Some data from nulliparous women has been presented earlier by the UK Amniotomy Group. MAIN OUTCOME MEASURES: Duration of labour, Apgar score, fetal morbidity and maternal morbidity including perineal injury, mode of delivery, epidural rates and the total number of vaginal examinations in the first stage of labour after amniotomy. INTERVENTIONS: Amniotomy at the next vaginal examination or amniotomy only if indicated. The median cervical dilatation at membrane rupture was 2 cm greater in the first group. RESULTS: A policy of routine amniotomy in labour had no measurable advantage over selective amniotomy for parous women (difference = 4 min) but shortened labour in nulliparous women by 1 h (Mann-Whitney U test: P < 0.05). There was a suggestion of a higher caesarean section rate (OR 1.9; 95% CI 0.9-3.5), and there were more vaginal examinations after membrane rupture in the group allocated routine amniotomy. There were no measurable differences in oxytocin use, fetal condition at birth, retained placenta rates, blood loss, pain or analgesia requirements. CONCLUSION: Routine amniotomy may shorten the first labour but not subsequent ones. There is a suggestion that routine surgical interference may be harmful by increasing the risk of caesarean section, and this agrees with data from other trials (common odds ratio 1.2; 95% CI 0.92-1.6).

Adult↗