Jessop Hospital

BACKGROUND AND METHODS: Small studies show that many children born as extremely preterm infants have neurologic and developmental disabilities. We evaluated all children who were born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland from March through December 1995 at the time when they reached a median age of 30 months. Each child underwent a formal assessment by an independent examiner. Development was evaluated with use of the Bayley Scales of Infant Development, and neurologic function was assessed by a standardized examination. Disability and severe disability were defined by predetermined criteria. RESULTS: At a median age of 30 months, corrected for gestational age, 283 (92 percent) of the 308 surviving children were formally assessed. The mean (+/-SD) scores on the Bayley Mental and Psychomotor Developmental Indexes, referenced to a population mean of 100, were 84+/-12 and 87+/-13, respectively. Fifty-three children (19 percent) had severely delayed development (with scores more than 3 SD below the mean), and a further 32 children (11 percent) had scores from 2 SD to 3 SD below the mean. Twenty-eight children (10 percent) had severe neuromotor disability, 7 (2 percent) were blind or perceived light only, and 8 (3 percent) had hearing loss that was uncorrectable or required aids. Overall, 138 children had disability (49 percent; 95 percent confidence interval, 43 to 55 percent), including 64 who met the criteria for severe disability (23 percent; 95 percent confidence interval, 18 to 28 percent). When data from 17 assessments by local pediatricians were included, 155 of the 314 infants discharged (49 percent) had no disability. CONCLUSIONS: Severe disability is common among children born as extremely preterm infants.

At coitus, human sperm are deposited into the anterior vagina, where, to avoid vaginal acid and immune responses, they quickly contact cervical mucus and enter the cervix. Cervical mucus filters out sperm with poor morphology and motility and as such only a minority of ejaculated sperm actually enter the cervix. In the uterus, muscular contractions may enhance passage of sperm through the uterine cavity. A few thousand sperm swim through the uterotubal junctions to reach the Fallopian tubes (uterine tubes, oviducts) where sperm are stored in a reservoir, or at least maintained in a fertile state, by interacting with endosalpingeal (oviductal) epithelium. As the time of ovulation approaches, sperm become capacitated and hyperactivated, which enables them to proceed towards the tubal ampulla. Sperm may be guided to the oocyte by a combination of thermotaxis and chemotaxis. Motility hyperactivation assists sperm in penetrating mucus in the tubes and the cumulus oophorus and zona pellucida of the oocyte, so that they may finally fuse with the oocyte plasma membrane. Knowledge of the biology of sperm transport can inspire improvements in artificial insemination, IVF, the diagnosis of infertility and the development of contraceptives.

OBJECTIVE: To evaluate the outcome for all infants born before 26 weeks of gestation in the United Kingdom and the Republic of Ireland. This report is of survival and complications up until discharge from hospital. METHODOLOGY: A prospective observational study of all births between March 1, 1995 and December 31, 1995 from 20 to 25 weeks of gestation. RESULTS: A total of 4004 births were recorded, and 811 infants were admitted for intensive care. Overall survival was 39% (n = 314). Male sex, no reported chorioamnionitis, no antenatal steroids, persistent bradycardia at 5 minutes, hypothermia, and high Clinical Risk Index for Babies (CRIB) score were all independently associated with death. Of the survivors, 17% had parenchymal cysts and/or hydrocephalus, 14% received treatment for retinopathy of prematurity (ROP), and 51% needed supplementary oxygen at the expected date of delivery. Failure to administer antenatal steroids and postnatal transfer for intensive care within 24 hours of birth were predictive of major scan abnormality; lower gestation was predictive of severe ROP, while being born to a black mother was protective. Being of lower gestation, male sex, tocolysis, low maternal age, neonatal hypothermia, a high CRIB score, and surfactant therapy were all predictive of oxygen dependency. Intensive care was provided in 137 units, only 8 of which had >5 survivors. There was no difference in survival between institutions when divided into quintiles based on their numbers of extremely preterm births or admissions. CONCLUSIONS: This study provides outcome data for this geographically defined cohort; survival and neonatal morbidity are consistent with previous data from the United Kingdom and facilitate comparison with other geographically based data.

Ninety six nulliparous women were investigated to establish whether childbirth causes damage to the striated muscles and nerve supply of the pelvic floor. The techniques used were concentric needle electromyography (EMG), pudendal nerve conduction tests and assessment of pelvic floor contraction using a perineometer. There was EMG evidence of re-innervation in the pelvic floor muscles after vaginal delivery in 80% of those studied. Women who had a long active second stage of labour and heavier babies showed the most EMG evidence of nerve damage. Forceps delivery and perineal tears did not affect the degree of nerve damage seen. We conclude that vaginal delivery causes partial denervation of the pelvic floor (with consequent re-innervation) in most women having their first baby. In a few this is severe and is associated with urinary and faecal incontinence. For some it is likely to be the first step along a path leading to prolapse and/or stress incontinence.

BACKGROUND: The prevalence of congenital uterine anomalies in women with reproductive failure remains unclear, largely due to methodological bias. The aim of this review is to assess the diagnostic accuracy of different methodologies and estimate the prevalence of congenital uterine anomalies in women with infertility and recurrent miscarriage (RM). METHODS: Studies from 1950 to 2007 were identified through a MEDLINE search; all relevant references were further reviewed. RESULTS: The most accurate diagnostic procedures are combined hysteroscopy and laparoscopy, sonohysterography (SHG) and possibly three-dimensional ultrasound (3D US). Two-dimensional ultrasound (2D US) and hysterosalpingography (HSG) are less accurate and are thus inadequate for diagnostic purposes. Preliminary studies (n = 24) suggest magnetic resonance imaging (MRI) is a relatively sensitive tool. A critical analysis of studies suggests that the prevalence of congenital uterine anomalies is approximately 6.7% [95% confidence interval (CI), 6.0-7.4] in the general population, approximately 7.3% (95% CI, 6.7-7.9) in the infertile population and approximately 16.7% (95% CI, 14.8-18.6) in the RM population. The arcuate uterus is the commonest anomaly in the general and RM population. In contrast, the septate uterus is the commonest anomaly in the infertile population, suggesting a possible association. CONCLUSIONS: Women with RM have a high prevalence of congenital uterine anomalies and should be thoroughly investigated. HSG and/or 2D US can be used as an initial screening tool. Combined hysteroscopy and laparoscopy, SHG and 3D US can be used for a definitive diagnosis. The accuracy and practicality of MRI remains unclear.

BACKGROUND: Obesity has become a major health problem worldwide and is also associated with adverse pregnancy outcome. The aim of this study was to assess the impact of obesity on the risk of miscarriage in the general public. METHODS: This was a nested case-control study. The study population was identified from a maternity database. Obese [body mass index (BMI) >30 kg/m2] women were compared with an age-matched control group with normal BMI (19-24.9 kg/m2). Only primiparous women were included in the study to avoid including the subject more than once, and to be able to correctly identify recurrent miscarriages. The prevalence of a previous history of early (6-12 weeks gestation), late (12-24 weeks gestation) and recurrent early miscarriages (REM) (more than three successive miscarriages <12 weeks) was compared between the two groups. RESULTS: A total of 1644 obese and 3288 age-matched normal weight controls with a mean age of 26.6 years [95% confidence interval (CI) 26.5-26.7] were included in the study. The risks of early miscarriage and REM were significantly higher among the obese patients (odds ratios 1.2 and 3.5, 95% CI 1.01-1.46 and 1.03-12.01, respectively; P = 0.04, for both]. CONCLUSIONS: Obesity is associated with increased risk of first trimester and recurrent miscarriage.

Intra-abdominal adhesion formation and reformation after surgery is a cause of significant morbidity, resulting in infertility and pain. The understanding of the pathogenesis of adhesion formation and reformation especially at the cellular and molecular level can help to further develop more effective treatments for the prevention of adhesion formation and reformation. Following an injury to the peritoneum, fibrinolytic activity over the peritoneal surface decreases, leading to changes in the expression and synthesis of various cellular mediators and in the remodelling of the connective tissue. The cellular response to peritoneal injury and adhesion formation and reformation are reviewed. Analysis of the available literature data on the cellular mediators in the peritoneal fluid showed variation in results from different investigators. The potential sources of variability and error are examined. It is still unclear if there is significant individual variation in the peritoneal response to injury.

BACKGROUND: Around 16% to 45% of adults have overactive bladder symptoms (urgency with frequency and/or urge incontinence - 'overactive bladder syndrome'). Anticholinergic drugs are common treatments. OBJECTIVES: To compare the effects of different anticholinergic drugs for overactive bladder symptoms. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 March 2011) and reference lists of relevant articles. SELECTION CRITERIA: Randomised trials in adults with overactive bladder symptoms or detrusor overactivity that compared one anticholinergic drug with another, or two doses of the same drug. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook. MAIN RESULTS: Eighty six trials, 70 parallel and 16 cross-over designs were included (31,249 adults). Most trials were described as double-blind, but were variable in other aspects of quality. Crossover studies did not present data in a way that could be included in the meta-analyses. Twenty nine collected quality of life data (the primary outcome measure) using validated measures, but only fifteen reported useable data.Tolterodine versus oxybutynin: There were no statistically significant differences for quality of life, patient reported cure or improvement, leakage episodes or voids in 24 hours, but fewer withdrawals due to adverse events with tolterodine (Risk Ratio (RR) 0.52, 95% confidence interval (CI) 0.40 to 0.66, data from eight trials), and less risk of dry mouth (RR 0.65, 95% CI 0.60 to 0.71, data from ten trials).Solifenacin versus tolterodine: There were statistically significant differences for quality of life (standardised mean difference (SMD) -0.12, 95% CI -0.23 to -0.01, data from three trials), patient reported cure/improvement (RR 1.25, 95% CI 1.13 to 1.39, data from two trials), leakage episodes in 24 hours (weighted mean difference (WMD) -0.30, 95% CI -0.53 to -0.08, data from four studies) and urgency episodes in 24 hours (WMD -0.43, 95% CI -0.74 to -0.13, data from four trials), all favouring solifenacin. There was no difference in withdrawals due to adverse events and dry mouth, but after sensitivity analysis the dry mouth (RR 0.69, 95% CI 0.51 to 0.94) was statistically significantly lower with solifenacin when compared to Immediate Release (IR) tolterodine.Fesoterodine versus extended release tolterodine: Three trials contributed to the meta analyses. There were statistically significant differences for quality of life (SMD -0.20, 95% CI -0.27 to -0.14), patient reported cure/improvement (RR 1.11, 95% CI 1.06 to 1.16), leakage episodes (WMD -0.19, 95% CI -0.30 to -0.09), frequency (WMD -0.27, 95% CI -0.47 to -0.06) and urgency episodes (WMD -0.44, 95% CI -0.72 to -0.16) in 24 hours, all favouring fesoterodine, but those taking fesoterodine had higher risk of withdrawal due to adverse events (RR 1.45, 95% CI 1.07 to 1.98) and higher risk of dry mouth (RR 1.80, 95% CI 1.58 to 2.05) at 12 weeks.Different doses of tolterodine: The standard recommended starting dose (2 mg twice daily) was compared with two lower (0.5 mg and 1 mg twice daily), and one higher dose (4 mg twice daily). The effects of 1 mg, 2 mg and 4 mg doses were similar for leakage episodes and micturitions in 24 hours, with greater risk of dry mouth with 2 and 4 mg doses at two to 12 weeks.Different doses of solifenacin: The standard recommended starting dose of 5 mg once daily was compared to 10 mg: while frequency and urgency were less (better) with 10 mg compared to 5 mg, there was a higher risk of dry mouth with 10 mg solifenacin at four to 12 weeks.Different doses of fesoterodine:The recommended starting dose of 4mg once daily was compared to 8 and 12 mg. The clinical efficacy (patient reported cure, leakage episodes, micturition per 24 hours) of 8 mg was better than 4 mg fesoterodine but with a higher risk of dry mouth with 8 mg.There was no statistically significant difference between 4 and 12 mg in the efficacy but the dry mouth was significantly higher with 12 mg at eight to 12 weeks.Extended versus immediate release preparations of oxybutynin and/or tolterodine: There were no statistically significant differences for cure/improvement, leakage episodes or micturitions in 24 hours, or withdrawals due to adverse events, but there were few data. Overall, extended release preparations had less risk of dry mouth at two to 12 weeks.One extended release preparation versus another: There was less risk of dry mouth with oral extended release tolterodine than oxybutynin (RR 0.75, 95% CI 0.59 to 0.95), but no difference between transdermal oxybutynin and oral extended release tolterodine although some people withdrew due to skin reaction at the transdermal patch site at 12 weeks. AUTHORS' CONCLUSIONS: Where the prescribing choice is between oral immediate release oxybutynin or tolterodine, tolterodine might be preferred for reduced risk of dry mouth. With tolterodine, 2 mg twice daily is the usual starting dose, but a 1 mg twice daily dose might be equally effective, with less risk of dry mouth. If extended release preparations of oxybutynin or tolterodine are available, these might be preferred to immediate release preparations because there is less risk of dry mouth.Between solifenacin and immediate release tolterodine, solifenacin might be preferred for better efficacy and less risk of dry mouth. Solifenacin 5 mg once daily is the usual starting dose, this could be increased to 10 mg once daily for better efficacy but with increased risk of dry mouth.Between fesoterodine and extended release tolterodine, fesoterodine might be preferred for superior efficacy but has higher risk of withdrawal due to adverse events and higher risk of dry mouth.There is little or no evidence available about quality of life, costs, or long-term outcome in these studies. There were insufficient data from trials of other anticholinergic drugs to draw any conclusions.

The concentration of leukaemia inhibitory factor (LIF) was measured in uterine flushings obtained from normal fertile women, from women with unexplained infertility and from women who suffered recurrent miscarriage. In normal fertile women, LIF was not detected in flushings obtained on days luteinizing hormone (LH)+0 to LH+6 of the cycle, but concentrations gradually increased from day LH+7 to a maximum at day LH+12. The amount of LIF in flushings obtained from women with unexplained infertility was significantly lower than in those from normal fertile women on day LH+10 (P < 0.05). The production of LIF by cultured human epithelial and stromal cells was also investigated. LIF was not detectable in the supernatants of cultured stromal cells. Basal LIF production by epithelial cells varied according to the stage in the cycle at which the biopsy was taken. Significantly more LIF was produced by epithelial cells from late proliferative and early secretory endometrium compared with amounts produced by cells from early proliferative (P < 0.001) and late secretory (P < 0.01) endometrium. High doses of progesterone and oestradiol caused a small decrease in epithelial cell LIF production: the combined effect of progesterone and oestradiol (P < 0.01) was greater than the effect of either steroid alone (P < 0.05). The results show, for the first time, the capability of human endometrium to produce LIF in vivo. The fact that maximum LIF concentrations are present at implantation and that decreased concentrations occur in women with unexplained infertility suggest the importance of this cytokine in embryo implantation.

BACKGROUND: Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes. METHODS: We did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m(2) or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30-39 vs ≥40 kg/m(2)). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843. FINDINGS: Between Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference -0·029, 95% CI -0·217 to 0·158; p=0·7597). The difference in the number of women reporting the combined adverse outcome of miscarriage, termination of pregnancy, stillbirth, or neonatal death in the metformin group (n=7) versus the placebo group (n=2) was not significant (odds ratio 3·60, 95% CI 0·74-17·50; p=0·11). INTERPRETATION: Metformin has no significant effect on birthweight percentile in obese pregnant women. Further follow-up of babies born to mothers in the EMPOWaR study will identify longer-term outcomes of metformin in this population; in the meantime, metformin should not be used to improve pregnancy outcomes in obese women without diabetes. FUNDING: The Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research partnership.

BACKGROUND: Rapid innate immune defences against infection involve the recognition of invading pathogens by specific pattern recognition receptors recently attributed to the family of Toll-like receptors (TLR). Little is known about the in vivo protein expression or distribution of TLR in the female reproductive tract in humans. It is likely that TLR distribution in the female reproductive tract reflects the immunological tolerance to the commensal organisms in lower parts of the tract (vagina, ectocervix and, partially, endocervix) and the intolerance to commensal microbial flora in the upper tract (the uterus and uterine tubes). METHODS: Using immunohistochemistry techniques, distribution of TLR1-6 was studied in surgical sections from the vagina, ecto- and endocervix, endometrium and uterine tubes, obtained from patients undergoing abdominal hysterectomy for benign gynaecological conditions. RESULTS: TLR1, 2, 3, 5 and 6 were present in the epithelia of different regions of female reproductive tract. However, TLR4 was only present in the endocervix, endometrium and uterine tubes and absent in vagina and ectocervix. In addition, a secretory form of TLR4 seems to be produced by the endocervical glands. CONCLUSION: TLR4 may play an important role in modulation of immunological tolerance in the lower parts of the female reproductive tract, and in host defence against ascending infection.

The symptoms typically associated with polycystic ovary syndrome (PCOS) such as acne, hirsutism, irregular menses, amenorrhoea, obesity and subfertility are a major source of psychological morbidity and can negatively affect quality of life (QoL). We systematically searched the literature to identify the impact of symptoms and treatments for PCOS on health-related QoL (HRQoL) and to report on the types and psychometric properties of the instruments used. Papers were retrieved by systematically searching four electronic databases and hand searching relevant reference lists and bibliographies. Nineteen papers used a standardized questionnaire to measure health status; of these 12 (63.2%) used generic tools and 8 (42%) used the disease-specific PCOS questionnaire. Although a meta-analysis was not possible, it appears that weight concerns have a particular negative impact upon HRQoL, although the role of body mass index in affecting HRQoL scores is inconclusive from the available evidence. Acne is the area least reported upon in terms of its impact upon HRQoL. With the exception of three studies, most of the research has focused upon adult women with PCOS. Despite the benefits of HRQoL measures in research, few are being used to evaluate the outcomes of treatment for PCOS upon the subjective health status of women with the condition.

Uterine fibroids are often found in women of reproductive age. Different types of fibroids may affect reproductive outcome to a different extent, with submucous, intramural and subserosal fibroids being (in decreasing order of importance) a cause of infertility and pregnancy wastage. Fibroids may also produce a number of complications during pregnancy. Women who are scheduled for assisted conception should be advised to have submucous and possibly intramural fibroids removed prior to IVF. Large fibroids (>5 cm), wherever their location, should be considered individually, with the reproductive history being an important consideration. Miscarriage rates are significantly reduced following myomectomy. Open myomectomy should be the route of choice when there are large subserosal or intramural fibroids, multiple fibroids or entry into the uterine cavity is to be expected. Proper assessment of the benefits and risks of surgery for individual patients should be carefully considered before offering a procedure.

Normal probability plots were used to assess the homogeneity of a population of 327 luteal phases from apparently ovulatory menstrual cycles. The length of the luteal phase was defined as the interval (in days) following but not including, the luteinizing hormone peak, up to and including the day before onset of menstruation. A small sub-set of the population consisted of cycles with abnormally short luteal phases but the majority of the data followed a normal frequency distribution which gave a mean (+/- SD) for normal luteal phase length of 14.13 (+/- 1.41) days. It was estimated that all cycles with a luteal phase less than or equal to 9 days were abnormal, and that 74%, 22% and 2% respectively of cycles with luteal phases of 10, 11 and 12 days were also abnormal. The total incidence of short luteal phases defined as above was 5.2%.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol and progesterone concentrations in plasma were obtained daily throughout the menstrual cycles of 94 regularly cycling women, aged between 24 and 50 years. Although mean LH concentrations changed little with advancing age, mean FSH concentrations were significantly (P less than 0.001) elevated from the age of 39 years. FSH concentrations in the oldest women studied (48-50 years) were approximately 3-fold greater than in the younger controls (women aged 23-35 years). LH concentrations rose slightly (P less than 0.05) during the last 5 years only. The increase in FSH concentration was not, however, uniform across the cycle, but was confined predominantly to the mid-follicular and post-ovulatory phases (i.e. those times in the normal menstrual cycle when circulating inhibin concentrations appear to be minimal). Despite the clear increases in FSH concentration, there was little alteration in the mean steroid profiles which remained within the normal fertile range throughout the last decade of reproductive life. The only exception to this was a small, transient, but significant (P less than 0.05) decrease in preovulatory oestradiol concentration between the ages of 36 and 38 years, which was followed by a transient increase (P less than 0.01) in oestradiol concentration between 39 and 44 years. However, no corresponding significant changes in mean progesterone concentrations were observed.

BACKGROUND: The aim of this meta-analysis was to investigate whether any difference exists in success rate of clinical outcomes of assisted reproductive technologies (ART) between women who actively smoke cigarettes at the time of treatment and those who do not. METHODS: An intensive computerized search was conducted on published literature from eight databases, using search terms related to smoking, assisted reproduction and outcome measures. Eligible studies compared outcomes of ART between cigarette smoking patients and a control group of non-smoking patients and reported on live birth rate per cycle, clinical pregnancy rate per cycle, ectopic pregnancy rate per pregnancy or spontaneous miscarriage rate per pregnancy, and 21 studies were included in the meta-analyses. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated for the data, and statistical heterogeneity was tested for using chi(2) and I(2) values. A systematic review examined the effect of smoking upon fertilization rates across 17 studies. RESULTS: Smoking patients demonstrated significantly lower odds of live birth per cycle (OR 0.54, 95% CI 0.30-0.99), significantly lower odds of clinical pregnancy per cycle (OR 0.56, 95% CI 0.43-0.73), significantly higher odds of spontaneous miscarriage (OR 2.65, 95% CI 1.33-5.30) and significantly higher odds of ectopic pregnancy (OR 15.69, 95% CI 2.87-85.76). A systematic literature review revealed that fertilization rates were not significantly different between smoking and non-smoking groups in most studies. CONCLUSIONS: This meta-analysis provides compelling evidence for a significant negative effect of cigarette smoking upon clinical outcomes of ART and should be presented to infertility patients who smoke cigarettes in order to optimize success rates.

BACKGROUND: Freedom from discrimination is one of the key principles in a human rights-based approach to maternal and newborn health. OBJECTIVE: To review the published evidence on discrimination against Romani women in maternity care in Europe, and on interventions to address this. SEARCH STRATEGY: A systematic search of eight electronic databases was undertaken in 2015 using the terms "Roma" and "maternity care". A broad search for grey literature included the websites of relevant agencies. DATA EXTRACTION AND SYNTHESIS: Standardised data extraction tables were utilised, quality was formally assessed and a line of argument synthesis was developed and tested against the data from the grey literature. RESULTS: Nine hundred papers were identified; three qualitative studies and seven sources of grey literature met the review criteria. These revealed that many Romani women encounter barriers to accessing maternity care. Even when they are able to access care, they can experience discriminatory mistreatment on the basis of their ethnicity, economic status, place of residence or language. The grey literature revealed some health professionals held underlying negative beliefs about Romani women. There were no published research studies examining the effectiveness of interventions to address discrimination against Romani women and their infants in Europe. The Roma Health Mediation Programme is a promising intervention identified in the grey literature. CONCLUSIONS: There is evidence of discrimination against Romani women in maternity care in Europe. Interventions to address discrimination against childbearing Romani women and underlying health provider prejudice are urgently needed, alongside analysis of factors predicting the success or failure of such initiatives.

Human embryonic stem (ES) cells offer substantial opportunities for providing well-defined differentiated cells for drug discovery, toxicology, and regenerative medicine, but the development of efficient techniques for their large-scale culture under defined conditions, and for controlling and directing their differentiation, presents a substantial challenge. Markers for defining the undifferentiated cells are well established, based upon previous studies of embryonal carcinoma (EC) cells, their malignant counterparts from teratocarcinomas. These provide valuable tools for monitoring human ES cultures and their state of differentiation. However, current culture techniques are suboptimal and involve the use of poorly defined culture media and the use of feeder cells. Over time, the cells may also acquire karyotypic changes, reflecting genetic selection and adaptation to in vitro culture conditions. Nevertheless, progress is being made. Originally, human ES cells were derived and maintained in medium containing fetal calf serum. They are now widely cultured in a proprietary serum-free formulation (serum replacement from Invitrogen Corp., Carlsbad, CA), and recently we have derived a new human ES line in this medium without fetal calf serum. Human fibroblasts can also be used to replace mouse embryo fibroblasts as feeder cells. We have now found it possible to culture a subline of human ES cells on Matrigel, or purified collagen type IV, laminin, and fibronectin, without feeders or feeder-conditioned medium. These cells nevertheless retain the features of undifferentiated human ES cells, including a capacity for differentiation. Although these cells also carried karyotypic changes, further research focused upon understanding the mechanisms that control self-renewal, apoptosis, and commitment to differentiation will facilitate the development of defined culture conditions that minimize genetic change and optimize the maintenance of the undifferentiated stem cells.

About a fifth of pregnancies end in miscarriage, leading to emotional consequences, such as anxiety and depression, which may last for a number of months. Despite this, women are not routinely provided with follow-up care. Anecdotal evidence suggests that follow-up focusing on emotional experiences may have beneficial effects. This study tests the hypothesis that the psychological debriefing process has a positive influence on emotional adaptation. Women were assessed, using the Hospital Anxiety and Depression Scale and Impact of Events Scale, at one week and four months post-miscarriage. Half the women also received psychological debriefing at two weeks. Intrusion and avoidance scores were initially as high as those of post-trauma victims, but had significantly decreased by four months. Depression was not detected at any time point, but anxiety was significantly higher than community sample estimates at one week and four months. Psychological debriefing was perceived to be helpful, but did not influence emotional adaptation. A number of hypotheses are provided to explain these results. Outcome scores at one week significantly predicted outcome at four months, suggesting that early assessment would be important in determining which women should be offered intervention.

BACKGROUND: Fertility preservation (FP) is an important quality of life issue for cancer survivors of reproductive age. Despite the existence of broad international guidelines, the delivery of oncofertility care, particularly amongst paediatric, adolescent and young adult patients, remains a challenge for healthcare professionals (HCPs). The quality of oncofertility care is variable and the uptake and utilization of FP remains low. Available guidelines fall short in providing adequate detail on how oncofertility models of care (MOC) allow for the real-world application of guidelines by HCPs. OBJECTIVE AND RATIONALE: The aim of this study was to systematically review the literature on the components of oncofertility care as defined by patient and clinician representatives, and identify the barriers, facilitators and challenges, so as to improve the implementation of oncofertility services. SEARCH METHODS: A systematic scoping review was conducted on oncofertility MOC literature published in English between 2007 and 2016, relating to 10 domains of care identified through consumer research: communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, training, supportive care during treatment, reproductive care after cancer treatment, psychosocial support and ethical practice of oncofertility care. A wide range of electronic databases (CINAHL, Embase, PsycINFO, PubMed, AEIPT, Education Research Complete, ProQuest and VOCED) were searched in order to synthesize the evidence around delivery of oncofertility care. Related citations and reference lists were searched. The review was undertaken following registration (International prospective register of systematic reviews (PROSPERO) registration number CRD42017055837) and guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). OUTCOMES: A total of 846 potentially relevant studies were identified after the removal of duplicates. All titles and abstracts were screened by a single reviewer and the final 147 papers were screened by two reviewers. Ten papers on established MOC were identified amongst the included papers. Data were extracted from each paper and quality scores were then summarized in the oncofertility MOC summary matrix. The results identified a number of themes for improving MOC in each domain, which included: the importance of patients receiving communication that is of a higher quality and in different formats on their fertility risk and FP options; improving provision of oncofertility care in a timely manner; improving access to age-appropriate care; defining the role and scope of practice of all HCPs; and improving communication between different HCPs. Different forms of decision aids were found useful for assisting patients to understand FP options and weigh up choices. WIDER IMPLICATIONS: This analysis identifies core components for delivery of oncofertility MOC. The provision of oncofertility services requires planning to ensure services have safe and reliable referral pathways and that they are age-appropriate and include medical and psychological oncofertility care into the survivorship period. In order for this to happen, collaboration needs to occur between clinicians, allied HCPs and executives within paediatric and adult hospitals, as well as fertility clinics across both public and private services. Training of both cancer and non-cancer HCPs is needed to improve the knowledge of HCPs, the quality of care provided and the confidence of HCPs with these consultations.