Ultrastructural cilia defects in multi-ciliated uterine glandular epithelial cells from women with reproductive failure.

In brief: The causes of subfertility and recurrent pregnancy loss are often unclear. This study shows that endometrial gland cilia from women with subfertility have ultrastructural defects. Abstract: Endometrial glands secrete products into the endometrium and are necessary for embryo implantation and successful pregnancy. However, structural and functional abnormalities in endometrial gland cilia from women with reproductive failure remain poorly understood. This was a cross-sectional study where endometrial biopsies were collected at days 19-23 of the menstrual cycle from women with unexplained recurrent pregnancy loss (n = 15), unexplained subfertility (n = 11) or from egg donor control participants (n = 10). Endometrial gland cilia ultrastructure was imaged by transmission electron microscopy and cilia defects assessed by an electron-microscopist from a national primary ciliary dyskinesia diagnostic centre. Endometrial glands were isolated, and the cilia beat frequency recorded by high speed video. Subfertile women have proportionately lower ultrastructurally normal cilia (P < 0.05); higher frequency of absent dynamin arms (P < 0.01) or inner arm defects (P < 0.01) and lower cilia beat frequency (P < 0.05). The mechanisms underlying these obversions have yet to be determined. Recent studies have identified cilia related gene expression changes associated with reproductive failure and this study adds to the growing body of literature revealing structural and functional changes. The observation that cilia defects occurred at a higher frequency in endometrial glands of subfertile women raises the question of its mechanistic role in implantation.

Discrete choice experiment exploring women's preferences in a novel device designed to monitor the womb environment and improve our understanding of reproductive disorders.

OBJECTIVES: The study aims to determine the relative importance of key attributes of a novel intrauterine device. The device monitors uterine oxygen, pH and temperature in real time with the aim of improving our understanding and treatment of reproductive disorders. DESIGN: A discrete choice experiment was used to elicit preferences in this novel investigative tool. The attributes and levels used in the choice scenarios were length of time using the device (7, 14 or 28 days), information obtained to guide treatment (limited, majority or all cases), risk of complications (1% or 10%) and discreteness (completely discrete, moderately discrete or indiscrete). SETTING: Secondary care hospital in Hampshire, UK. PARTICIPANTS: 361 women of reproductive age. PRIMARY AND SECONDARY OUTCOME MEASURES: Conditional logit and latent class logit regression models to determine the preference for each attribute. RESULTS: Conditional logit coefficients allow comparison between attributes; women placed most importance on obtaining information to guide treatment in all cases (2.771), followed by having a completely discrete device (1.104), reducing risk of complications by 1% (0.184) and decreased length of time by 1 day (0.0150). All coefficients p<0.01. Latent class conditional logit assigns participants to two classes with 27.4% in class 1 who are less likely to have higher education or qualify for National Health Service-funded in vitro fertilisation compared with class 2. Those in class 2 placed 1.7 times more importance on a device whose information guided treatment in all cases and a 1% decrease in complications risk was nearly 15 times more attractive. CONCLUSIONS: Women placed most importance on having a device that obtains information to guide treatment and are willing to use the device for a longer, have a device with higher risk of complications and an indiscrete device if it is able to provide answers and direction for treatment of their reproductive disorder.

Smartphone-based lifestyle coaching modifies behaviours in women with subfertility or recurrent miscarriage: a randomized controlled trial.

RESEARCH QUESTION: Is an online lifestyle coaching platform more effective at modifying periconceptional behaviours than standard advice offered by the UK National Health Service (NHS)? DESIGN: Women with subfertility or recurrent miscarriage were recruited to a two-centre randomized controlled trial. They were randomized to either the online lifestyle coaching platform Smarter Pregnancy (intervention) or periconceptional advice provided by NHS websites (control). Participants completed a lifestyle questionnaire at baseline, 6, 12, 18 and 24 weeks, and the results were used to tailor lifestyle coaching in the intervention group. At baseline, 12 and 24 weeks, composite risk scores (CRS) were calculated. A lower CRS corresponds to a healthier lifestyle. RESULTS: Of the 400 women recruited, 262 women were randomized (131 in each arm). At 12 weeks, a reduction in CRS (includes risk score for intake of folic acid, vegetables and fruits, smoking and alcohol) was observed in the intervention versus control arms. After correcting for baseline, the difference in the CRS between intervention and control was -0.47 (95% CI -0.97 to 0.02) at 12 weeks and -0.32 (95% CI -0.82 to 0.15) at 24 weeks. A statistically significant reduction in lifestyle risk scores was found in women with a body mass index (BMI) of 25 kg/m2 or above compared with those with a BMI below 25kg/m2. The odds of being pregnant at 24 weeks was increased in the intervention versus control (OR 2.83, 95% CI 0.35 to 57.76). CONCLUSIONS: The Smarter Pregnancy coaching platform is more effective in delivering lifestyle advice and modulating behaviours to support women with a history of subfertility or recurrent miscarriage than standard online NHS advice.

Systematic review and meta-analysis of female lifestyle factors and risk of recurrent pregnancy loss.

It is known that lifestyle factors affect sporadic miscarriage, but the extent of this on RPL (recurrent pregnancy loss) is less well known. A systematic review and meta-analysis was performed to assess the associations between lifestyle factors and RPL. Studies that analysed RPL in the context of BMI, smoking, alcohol and caffeine intake were included. The primary and secondary outcomes were odds of having RPL in the general population and odds of further miscarriage, respectively. Underweight and women with BMI > 25 are at higher odds of RPL in the general population (OR 1.2, 95% CI 1.12-1.28 and OR 1.21, 95% CI 1.06-1.38, respectively). In women with RPL, having BMI > 30 and BMI > 25 has increased odds of further miscarriages (OR 1.77, 95% CI 1.25-2.50 and OR 1.35, 95% CI 1.07-1.72, respectively). The quality of the evidence for our findings was low or very low. Being underweight and BMI > 25 contributes significantly to increased risk of RPL (general population). BMI > 25 or BMI > 30 increases the risk of further miscarriages (RPL population). Larger studies addressing the effects of alcohol, cigarette smoking and caffeine on the risk of RPL with optimisation of BMI in this cohort of women are now needed.

A modified arginine-depleting enzyme NEI-01 inhibits growth of pancreatic cancer cells.

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.

Laparoscopic ovarian drilling for ovulation induction in women with anovulatory polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition affecting 8% to 13% of reproductive-aged women. In the past clomiphene citrate (CC) used to be the first-line treatment in women with PCOS. Ovulation induction with letrozole should be the first-line treatment according to new guidelines, but the use of letrozole is off-label. Consequently, CC is still commonly used. Approximately 20% of women on CC do not ovulate. Women who are CC-resistant can be treated with gonadotrophins or other medical ovulation-induction agents. These medications are not always successful, can be time-consuming and can cause adverse events like multiple pregnancies and cycle cancellation due to an excessive response. Laparoscopic ovarian drilling (LOD) is a surgical alternative to medical treatment. There are risks associated with surgery, such as complications from anaesthesia, infection, and adhesions. OBJECTIVES: To evaluate the effectiveness and safety of LOD with or without medical ovulation induction compared with medical ovulation induction alone for women with anovulatory polycystic PCOS and CC-resistance. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group (CGFG) trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers up to 8 October 2019, together with reference checking and contact with study authors and experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women with anovulatory PCOS and CC resistance who underwent LOD with or without medical ovulation induction versus medical ovulation induction alone, LOD with assisted reproductive technologies (ART) versus ART, LOD with second-look laparoscopy versus expectant management, or different techniques of LOD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, extracted data and evaluated the quality of the evidence using the GRADE method. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS), ovulation, costs, and quality of life were secondary outcomes. MAIN RESULTS: This updated review includes 38 trials (3326 women). The evidence was very low- to moderate-quality; the main limitations were due to poor reporting of study methods, with downgrading for risks of bias (randomisation and allocation concealment) and lack of blinding. Laparoscopic ovarian drilling with or without medical ovulation induction versus medical ovulation induction alone Pooled results suggest LOD may decrease live birth slightly when compared with medical ovulation induction alone (odds ratio (OR) 0.71, 95% confidence interval (CI) 0.54 to 0.92; 9 studies, 1015 women; I2 = 0%; low-quality evidence). The evidence suggest that if the chance of live birth following medical ovulation induction alone is 42%, the chance following LOD would be between 28% and 40%. The sensitivity analysis restricted to only RCTs with low risk of selection bias suggested there is uncertainty whether there is a difference between the treatments (OR 0.90, 95% CI 0.59 to 1.36; 4 studies, 415 women; I2 = 0%, low-quality evidence). LOD probably reduces multiple pregnancy rates (Peto OR 0.34, 95% CI 0.18 to 0.66; 14 studies, 1161 women; I2 = 2%; moderate-quality evidence). This suggests that if we assume the risk of multiple pregnancy following medical ovulation induction is 5.0%, the risk following LOD would be between 0.9% and 3.4%. Restricting to RCTs that followed women for six months after LOD and six cycles of ovulation induction only, the results for live birth were consistent with the main analysis. There may be little or no difference between the treatments for the likelihood of a clinical pregnancy (OR 0.86, 95% CI 0.72 to 1.03; 21 studies, 2016 women; I2 = 19%; low-quality evidence). There is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage (OR 1.11, 95% CI 0.78 to 1.59; 19 studies, 1909 women; I2 = 0%; low-quality evidence). OHSS was a very rare event. LOD may reduce OHSS (Peto OR 0.25, 95% CI 0.07 to 0.91; 8 studies, 722 women; I2 = 0%; low-quality evidence). Unilateral LOD versus bilateral LOD Due to the small sample size, the quality of evidence is insufficient to justify a conclusion on live birth (OR 0.83, 95% CI 0.24 to 2.78; 1 study, 44 women; very low-quality evidence). There were no data available on multiple pregnancy. The likelihood of a clinical pregnancy is uncertain between the treatments, due to the quality of the evidence and the large heterogeneity between the studies (OR 0.57, 95% CI 0.39 to 0.84; 7 studies, 470 women; I2 = 60%, very low-quality evidence). Due to the small sample size, the quality of evidence is not sufficient to justify a conclusion on miscarriage (OR 1.02, 95% CI 0.31 to 3.33; 2 studies, 131 women; I2 = 0%; very low-quality evidence). Other comparisons Due to lack of evidence and very low-quality data there is uncertainty whether there is a difference for any of the following comparisons: LOD with IVF versus IVF, LOD with second-look laparoscopy versus expectant management, monopolar versus bipolar LOD, and adjusted thermal dose versus fixed thermal dose. AUTHORS' CONCLUSIONS: Laparoscopic ovarian drilling with and without medical ovulation induction may decrease the live birth rate in women with anovulatory PCOS and CC resistance compared with medical ovulation induction alone. But the sensitivity analysis restricted to only RCTs at low risk of selection bias suggests there is uncertainty whether there is a difference between the treatments, due to uncertainty around the estimate. Moderate-quality evidence shows that LOD probably reduces the number of multiple pregnancy. Low-quality evidence suggests that there may be little or no difference between the treatments for the likelihood of a clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. LOD may result in less OHSS. The quality of evidence is insufficient to justify a conclusion on live birth, clinical pregnancy or miscarriage rate for the analysis of unilateral LOD versus bilateral LOD. There were no data available on multiple pregnancy.

Medical students' experiences of the benefits and influences regarding a placement mentoring programme preparing them for future practice as junior doctors: a qualitative study.

OBJECTIVE: To study medical students' views and experiences of the benefits and influences regarding a mentoring programme aimed at preparing them for future practice as a doctor during their Obstetrics and Gynaecology (O&G) placement in a UK teaching hospital. DESIGN: A qualitative approach, employing focus groups and thematic analysis. SETTING: Single-centre UK Teaching hospital. PARTICIPANTS: Thirteen undergraduate medical students at the University of Southampton who had completed their standard 8-week placement in O&G and had been assigned a mentor throughout. MAIN OUTCOME MEASURES: Medical students' experiences and perceptions of the benefits and influences of having a mentor throughout their O&G placement. RESULTS: From our data, four central themes were identified: integration, feedback, seniority and expectations. Students found mentorship useful for integration into the team, and an opportunity for constructive feedback on their clinical skills and professional skills for example, communication and team-working. Seniority and the level of contact of their mentor was the main reason for differing mentoring experiences: although senior mentors spent less time with their mentees, they were able to offer more careers advice. Students felt that the mentors and mentees were not always clear on the expectations of the mentoring programme. CONCLUSIONS: Mentorship may be a useful addition to help prepare students for future clinical practice. Mentor training may improve consistency of experiences. This study demonstrates that a mentoring programme is deliverable and widely accepted by medical students in a clinical placement such as O&G, and may have wider benefits if introduced on a regional/national level.

Hydrosalpinx - Salpingostomy, salpingectomy or tubal occlusion.

Tubal factors account for approximately 25% of cases of infertility, and the most severe manifestation of tubal disease is hydrosalpinx, accounting for 10-30% of tubal diseases. Hydrosalpinx is a distension or dilatation of the fallopian tube in the presence of a distal tubal occlusion, and the most common cause is pelvic inflammatory disease. Women with hydrosalpinges have lower implantation and pregnancy rates in assisted reproductive technology (ART), due to a combination of mechanical and chemical factors thought to disrupt the endometrial environment. Current guidance is removal of the tube by salpingectomy (preferably laparoscopically) before IVF treatment. Salpingostomy, or distal tubal plastic surgery in the management of hydrosalpinx, is an alternative for women desiring natural conception, although ectopic pregnancy rates as high as 10% have been reported. Proximal tubal occlusion with Essure® devices placed hysteroscopically can be considered particularly in cases of distorted pelvic anatomy or pelvic adhesions making abdominal surgery complex. However, low clinical pregnancy and live birth rates have been reported with the use of these devices before IVF. In this review, we discuss salpingostomy, salpingectomy and tubal occlusion as possible management options for the reproductive women with hydrosalpinx.

A randomised controlled trial of a personalised lifestyle coaching application in modifying periconceptional behaviours in women suffering from reproductive failures (iPLAN trial).

BACKGROUND: Lifestyle, in particular obesity and smoking has significant impacts on fertility and an important focus for the treatment of reproductive failures is the optimisation of periconceptional lifestyle behaviours. The preimplantation intrauterine environment within the uterus is also key for embryo development and early programming. Although the benefits a healthy periconceptional lifestyle are well described, there remains a paucity of data demonstrating the efficacy of interventions designed to optimise preconceptional lifestyle behaviours and choices. METHODS: This study is a prospective randomised controlled trial which aims to address the question of whether an online personalised lifestyle coaching application is an effective means of delivering periconceptional advice in women suffering from reproductive failures. Women suffering from subfertility or recurrent miscarriages attending the outpatient clinic will be randomised into either the intervention arm (personalised online lifestyle coaching application) or the control arm (standard periconceptional advice including information from NHS websites). Both groups will be asked to complete a validated lifestyle questionnaire at baseline, and 6, 12, 18 and 24 weeks after randomisation. The primary outcome is the composite dietary and lifestyle risk score at 12 weeks. The secondary outcomes will include compliance with the program, proportion achieving spontaneous conception during the study period and the dietary and lifestyle risk score at 24 weeks. DISCUSSION: With this study, we aim to clarify whether a personalised online based lifestyle coaching application is more effective at improving behaviours than standard advice offered by National Health Service (NHS) resources. A personalised lifestyle coaching application may represent an empowering and cost effective means of delivering periconceptional advice in women with subfertility or recurrent miscarriages. TRIAL REGISTRATION: The iPLAN trial was retrospectively registered ( ISRCTN 89523555 ).

Is infant arterial stiffness associated with maternal blood pressure in pregnancy? Findings from a UK birth cohort (Baby VIP study).

BACKGROUND: In adults, arterial stiffness measured by pulse wave velocity (PWV) is regarded as a predictor of cardiovascular disease. Infant vascular development depends on factors related to pregnancy, including maternal blood pressure (BP). This study assessed the association between maternal BP in pregnancy and infant brachio-femoral PWV at age 2-6 weeks. METHODS: The Baby Vascular health and Iron in Pregnancy (Baby VIP) study is a birth cohort which measured PWV and heart rate (HR) in 284 babies in Leeds, UK, at 2-6 weeks after birth. Maternal BP measurements at 12 and 36 weeks gestation was collected from antenatal clinical records. Multivariable linear regression models assessed associations between maternal systolic and diastolic BPs, and BP change from booking to 36 weeks, with infant PWV adjusting for covariables at both mother and baby level. RESULTS: There was no evidence of an association between infant PWV and maternal systolic BP at booking (adjusted regression coefficient -0.01 m/s per 10mmHg, 95% CI -0.11, 0.14, p = 0.84) or at 36 weeks (adjusted regression coefficient 0.00 m/s per 10mmHg, 95% CI -0.12, 0.11, p = 0.95). Change between 12 and 36 weeks gestation of more than 30 mmHg in systolic BP or 15 mmHg in diastolic BP was also not associated with infant PWV. There was an inverse relationship between infant HR and infant PWV (regression coefficient -0.14 m/s per 10 bpm, 95% CI -0.22, -0.05, p<0.01). CONCLUSIONS: This study has shown no evidence of association between infant PWV at 2-6 weeks of age and maternal BP in early or late pregnancy. Infant HR was inversely associated with infant PWV. Further studies are required to determine the predictors of infant PWV as well as the importance and long term implications of PWV measurements in infants.

In vivo oxygen, temperature and pH dynamics in the female reproductive tract and their importance in human conception: a systematic review.

BACKGROUND: Despite advances in ART, implantation and pregnancy rates per embryo transfer still remain low. IVF laboratories strive to ensure that the process of handling gametes in vitro closely mimics the in vivo environment. However, there remains a lack of knowledge regarding the in vivo regulation and dynamic variation in biophysical parameters such as oxygen concentration, pH and temperature within the reproductive tract. OBJECTIVE AND RATIONALE: To undertake a systematic review of the current understanding of the physico-chemical parameters of oxygen tension (pO2), pH and temperature within the female reproductive tract, and their potential implications in clinical and pathological processes related to fertility and those pertaining to limited reproductive capacity. SEARCH METHODS: A comprehensive literature search was performed using electronic databases including Medline, Embase, Cochrane Library and Pubmed to identify original and review articles addressing the biophysical parameters (pO2, pH and temperature) in the female reproductive tract of any species. The search included all studies published between 1946 and November 2015. Search terms included 'oxygen', 'pH', 'hydrogen ion concentration', 'acid base' and others terms. We also used special features and truncations to identify synonyms and broaden the search. Studies were excluded if they only assessed embryo culture conditions, fetal acid-base status, oxidative stress, outcomes of pregnancy and measurements of these parameters in non-reproductive organs. OUTCOMES: Our search generated 18 685 records and 60 articles were included. pO2 within the female reproductive tract shows cyclical variation and minute-to-minute oscillations, which may be influenced by uterine contractility, hormones, the autonomic system, cardiac pulsatility, and myometrial and smooth muscle integrity. Fine balanced control of pO2 and avoidance of overwhelming oxidative stress is crucial for embryogenesis and implantation. The pH in the female reproductive tract is graduated, with lowest pH in the vagina (~pH 4.42) increasing toward the Fallopian tubes (FTs) (~pH 7.94), reflecting variation in the site-specific microbiome and acid-base buffering at the tissue/cellular level. The temperature variation in humans is cyclical by day and month. In humans, it is biphasic, increasing in the luteal phase; with the caudal region of the oviduct 1-2 degrees cooler than the cranial portion. Temperature variation is influenced by hormones, density of pelvic/uterine vascular beds and effectiveness of heat exchange locally, crucial for sperm motility and embryo development. We have identified significant deficiencies and inconsistencies in the methods used to assess these biophysical factors within the reproductive tract. We have suggested that the technological solutions including the development of methods and models for real time, in vivo recordings of biophysical parameters. WIDER IMPLICATIONS: The notion of 'back to nature' in assisted conception suggested 20 years ago has yet to be translated into clinical practice. While the findings from this systematic review do not provide evidence to change current in vitro protocols, it highlights our current inability to assess the in vivo reproductive tract environment in real time. Data made available through future development of sensing technology in utero may help to provide new insights into how best to optimize the in vitro embryo environment and allow for more precise and personalized fertility treatment.

Implementation of a teaching programme to improve doctors' awareness of DVLA guidelines: a multicentre study.

INTRODUCTION: Over half of the UK population holds a driver's licence. Driver and Vehicle Licensing Authority (DVLA) guidelines are available for conditions from most specialties. Despite this, no focused training occurs in the undergraduate or postgraduate setting. We evaluate the impact of a teaching programme to improve guideline awareness. METHODS: A 25-point questionnaire was designed using the current DVLA guidelines. Five questions were included for the following fields: neurology, cardiology, drug and alcohol abuse, visual disorders and respiratory. This was distributed to doctors in training at five hospitals. Four weeks later, a single-session teaching programme was implemented. The questionnaire was redistributed. Preintervention and postintervention scores were compared using the Wilcoxon rank sum test. RESULTS: 139 preteaching and 144 post-teaching questionnaires were completed. Implementation of a single-session teaching programme significantly improved the knowledge of DVLA guidelines in all five areas explored. Median scores: neurology, preteaching 40%, post-teaching 100%, p<0.001; cardiology, 0%, 100%, p<0.001; drug and alcohol misuse, 0%, 100%, p<0.001; visual disorders, 40%, 100%, p<0.001; respiratory disorders, 20%, 100%, p<0.001; and overall, 28%, 92%, p<0.001. CONCLUSIONS: Knowledge of DVLA guidelines among our cohort was poor. Implementation of a single-session teaching programme can significantly improve guideline knowledge and awareness, serving as a cost-effective intervention.

Immediate referral to colposcopy versus cytological surveillance for low-grade cervical cytological abnormalities in the absence of HPV test: A systematic review and a meta-analysis of the literature.

We performed a systematic review and meta-analysis to explore the optimum management strategy for women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/mild dyskaryosis) cytological abnormalities at primary screening in the absence of HPV DNA test. We searched MEDLINE, EMBASE and CENTRAL and included randomised controlled trials comparing immediate colposcopy to cytological surveillance in women with ASCUS/LSIL. The outcomes of interest were occurrence of different histological grades of cervical intraepithelial neoplasia (CIN) and default rates during follow-up. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect model and with inverse variance weighting. Interstudy heterogeneity was assessed using I2 statistics. Six RCTs were included. Immediate colposcopy significantly increased detection of unimportant abnormalities as opposed to repeat cytology (koilocytosis: 32 vs. 21%, RR: 1.49, 95% CI = 1.17-1.90); CIN1: 21 vs. 8%, RR: 2.58, 95% CI = 1.69-3.94). Although immediate colposcopy detected CIN2, CIN2+, and CIN3+ earlier than cytology, the differences were no longer observed at 24 months (CIN3+: 10.3 vs.11.9%, RR: 1.02, 95% CI = 0.53-1.97), with significant interstudy heterogeneity (p < 0.001, I2  = 93%). Default risk was significantly higher for repeat cytology (6 months: 6.3 vs. 13.3%, RR: 3.85, 95% CI = 1.27-11.63; 12 months: 6.3 vs. 14.8%, RR: 6.39, 95% CI = 1.24-32.95; 24 months: 0.9 vs. 16.1%, RR: 19.1, 95% CI = 9.02-40.4). Detection of CIN2+ for cytological surveillance over two years is similar to that of immediate colposcopy, although patients may default. Colposcopy may be first choice when good compliance is not assured, but may increase detection of insignificant lesions. This emphasizes the need for a reflex triage test to distinguish women who need diagnostic work-up from those who can return to routine recall.

Negative pressure wound therapy aids recovery following surgical debridement due to severe bacterial cellulitis with abdominal abscess post-cesarean: A case report (CARE-Compliant).

INTRODUCTION: Bacterial cellulitis post-Cesarean section is rare. Negative pressure wound therapy (NPWT) is widely used in various medical specialities; its effectiveness in obstetrics however remains the topic of debate-used predominantly as an adjunct to secondary intention specific to high-risk patient groups. Its application in the treatment of actively infected wounds post-Cesarean is not well documented. Here, we document NPWT in the treatment of an unusually severe case of bacterial cellulitis with abdominal abscess postpartum. We provide a unique photographic timeline of wound progression following major surgical debridement, documenting the effectiveness of 2 different NPWT systems (RENASYS GO and PICO, Smith & Nephew). We report problems encountered using these NPWT systems and "ad-hoc" solutions to improve efficacy and patient experience.A 34-year-old primiparous Caucasian female with no prior history or risk factors for infection and a normal body mass index (BMI) presented with severe abdominal pain, swelling, and extensive abdominal redness 7 days postemergency Cesarean section. Examination revealed extensive cellulitis with associated abdominal abscess. Staphylococcus aureus was identified in wound exudates and extensive surgical debridement undertaken day 11 postnatally due to continued febrile episodes and clinical deterioration, despite aggressive intravenous antibiotic therapy. Occlusive NPWT dressings were applied for a period of 3 weeks before discharge, as well as a further 5 weeks postdischarge into the community.NPWT was well tolerated and efficacious in infection clearance and wound healing during bacterial cellulitis. Wound healing averaged 1 cm per week before NPWT withdrawal; cessation of NPWT before full wound closure resulted in significantly reduced healing rate, increased purulent discharges, and skin irritation, highlighting the efficacy of NPWT. Five-month follow-up in the clinic found the wound to be fully healed with no additional scarring beyond the boundaries of the original Cesarean incision. The patient was pleased with treatment outcomes, reporting no lasting pain or discomfort from the scar. CONCLUSIONS: This report represents the first documented use of NPWT to aid healing of an actively infected, open wound following extensive surgical debridement 10 days post-Cesarean section, confirming both the efficacy and tolerability of NPWT for the treatment of severe bacterial cellulitis in obstetric debridement.

Prediction of an estimated delivery date should take into account both the length of a previous pregnancy and the interpregnancy interval.

OBJECTIVE: To assess the relationship between gestational lengths of the first and second pregnancies in the same women. STUDY DESIGN: Observational study. METHODS: We used information from a dataset of over 500,000 pregnancies from 15 maternity units in the North West Thames, London. Data on the gestational length in days of the first pregnancy and the gestational length in days of the second pregnancy were correlated using regression models. First and second pregnancies were ascribed to the same women by identical maternal date of birth, ethnicity and maternal height (to within ±3cm). RESULTS: There is a statistically significant cubic relationship between the gestational lengths of the first birth and the second birth (R 0.102, p<0.001). The gestational length of the second pregnancy is likely to be closer to 280 days than the first pregnancy. In the 20% of women who had an interpregnancy interval of less than one year, the next pregnancy was one day shorter for every three months less than 12. CONCLUSIONS: Although the gestation of second pregnancies exhibits regression towards the mean of 280 days, there is still a clinically important tendency for both preterm and postdates pregnancies to recur. Prediction of an estimated delivery date for second pregnancies should take into account both the length of the first pregnancy and the interpregnancy interval if it is less than 12 months.

Plasmid-Mediated OqxAB Is an Important Mechanism for Nitrofurantoin Resistance in Escherichia coli.

Increasing consumption of nitrofurantoin (NIT) for treatment of acute uncomplicated urinary tract infections (UTI) highlights the need to monitor emerging NIT resistance mechanisms. This study investigated the molecular epidemiology of the multidrug-resistant efflux gene oqxAB and its contribution to nitrofurantoin resistance by using Escherichia coli isolates originating from patients with UTI (n = 205; collected in 2004 to 2013) and food-producing animals (n = 136; collected in 2012 to 2013) in Hong Kong. The oqxAB gene was highly prevalent among NIT-intermediate (11.5% to 45.5%) and -resistant (39.2% to 65.5%) isolates but rare (0% to 1.7%) among NIT-susceptible (NIT-S) isolates. In our isolates, the oqxAB gene was associated with IS26 and was carried by plasmids of diverse replicon types. Multilocus sequence typing revealed that the clones of oqxAB-positive E. coli were diverse. The combination of oqxAB and nfsA mutations was found to be sufficient for high-level NIT resistance. Curing of oqxAB-carrying plasmids from 20 NIT-intermediate/resistant UTI isolates markedly reduced the geometric mean MIC of NIT from 168.9 µg/ml to 34.3 µg/ml. In the plasmid-cured variants, 20% (1/5) of isolates with nfsA mutations were NIT-S, while 80% (12/15) of isolates without nfsA mutations were NIT-S (P = 0.015). The presence of plasmid-based oqxAB increased the mutation prevention concentration of NIT from 128 µg/ml to 256 µg/ml and facilitated the development of clinically important levels of nitrofurantoin resistance. In conclusion, plasmid-mediated oqxAB is an important nitrofurantoin resistance mechanism. There is a great need to monitor the dissemination of this transferable multidrug-resistant efflux pump.

Spontaneous Expulsion of Intramural Fibroid Six Weeks after Emergency Caesarean Section.

We present a thirty-six-year-old woman with a high risk pregnancy, complicated by multiple congenital anomalies, severe hyperemesis, a pulmonary embolus, and a large intramural fibroid. This fibroid grew in size during the pregnancy. At 34 + 5 weeks, there were reduced fetal movements and a pathological CTG. A live infant was delivered by an emergency cesarean section. Five weeks postpartum, she presented with abdominal pain, offensive vaginal discharge, and fevers. She was given antibiotics and ferrous sulphate. An abdominal ultrasound showed an 11 × 12 × 9 cm fibroid with a coarse degenerative appearance. Clinically, she showed signs of sepsis; a CT scan and laparotomy performed under general anesthetic did not find any collections as a source of sepsis. When stable, she was discharged. She re-presented two days later with a large mass (necrotic fibroid) in her vagina. This is the first case of spontaneous expulsion of fibroid six weeks after caesarean section. Presentation of pain and fever after the delivery may be due to red degeneration of the fibroid, caused by diminished blood supply, ischaemia, and necrosis. This case highlights the importance of considering fibroids as a cause for abdominal pain during and after pregnancy, even up to 6 weeks after delivery.

The effect of economic downturns on maternal mortality among pregnancies with abortive outcomes in 81 countries, 1981-2010.

OBJECTIVE: To determine the association between economic downturns and abortion-related maternal mortality in multiple countries over 30 years. METHODS: In a retrospective study, WHO data were obtained for maternal deaths among pregnancies with abortive outcomes between January 1, 1981, and December 31, 2010. Economic data for the same period were obtained from The World Bank. An economic downturn was defined as an annual decline in gross domestic product per head. Multivariate regression-controlling for country-specific differences in infrastructure, population size, and demographic structure-and 5-year lag analyses were performed. RESULTS: Data were available for 81 countries. Abortion-related maternal mortality was significantly increased in years of economic downturns (R=0.0708; 95% confidence interval [CI] 0.0264-0.1151; P=0.0018). The association was sustained for 4 years after an economic downturn (year 1: R=0.0709 [95% CI 0.0231-0.1187], P=0.0037; year 2: R=0.0634 [0.0178-0.1089], P=0.0065; year 3: R=0.0554 [0.0105-0.1004], P=0.0157; year 4: R=0.0593 [0.0148-0.1037], P=0.009). There was an annual 36% increase in deaths associated with unsafe abortion during economic downturn years. CONCLUSION: Economic downturns were associated with increased abortion-related maternal mortality, possibly due to changes in government healthcare spending and service provision. A global economic downturn could impede a reduction in maternal mortality.

Government health care spending and child mortality.

BACKGROUND: Government health care spending (GHS) is of increasing importance to child health. Our study determined the relationship between reductions in GHS and child mortality rates in high- and low-income countries. METHODS: The authors used comparative country-level data for 176 countries covering the years 1981 to 2010, obtained from the World Bank and the Institute for Health Metrics and Evaluation. Multivariate regression analysis was used to determine the association between changes in GHS and child mortality, controlling for differences in infrastructure and demographics. RESULTS: Data were available for 176 countries, equating to a population of ∼ 5.8 billion as of 2010. A 1% decrease in GHS was associated with a significant increase in 4 child mortality measures: neonatal (regression coefficient [R] 0.0899, P = .0001, 95% confidence interval [CI] 0.0440-0.1358), postneonatal (R = 0.1354, P = .0001, 95% CI 0.0678-0.2030), 1- to 5-year (R = 0.3501, P < .0001, 95% CI 0.2318-0.4685), and under 5-year (R = 0.5207, P < .0001, 95% CI 0.3168-0.7247) mortality rates. The effect was evident up to 5 years after the reduction in GHS (P < .0001). Compared with high-income countries, low-income countries experienced greater deteriorations of ∼ 1.31 times neonatal mortality, 2.81 times postneonatal mortality, 8.08 times 1- to 5-year child mortality, and 2.85 times under 5-year mortality. CONCLUSIONS: Reductions in GHS are associated with significant increases in child mortality, with the largest increases occurring in low-income countries.