Antenatal thiopurine exposure in women with IBD is associated with intrahepatic cholestasis of pregnancy.

BACKGROUND: Pregnant women with inflammatory bowel disease (IBD) continue thiopurines to maintain remission. Other studies have reported intrahepatic cholestasis of pregnancy (ICP) in IBD pregnancies exposed to thiopurines. We aimed to investigate whether thiopurines are associated with an increased risk of ICP. RESEARCH DESIGN AND METHODS: Single-center retrospective cohort study comparing incidence of ICP in thiopurine-exposed versus non-exposed patients with IBD compared with age-matched pregnant controls. RESULTS: The IBD cohort consisted of 386 pregnancies in 243 patients with IBD, with 386 age-matched controls. In patients with IBD, ICP was significantly more common among thiopurine-exposed pregnancies (9.0% vs 1.8%; odds ratio [95% confidence interval] = 5.34 [1.78-16.02]; p = 0.021). IBD patients with thiopurine exposure were significantly more likely to experience ICP compared to non-IBD controls (9.0% vs 1.3%; p < 0.001). Patients with IBD not exposed to thiopurines had a comparable ICP incidence with controls (1.8% vs 1.3%; p = 0.75). Severe ICP occurred in 80% of thiopurine-exposed ICP cases versus 40% in non-exposed (p = 0.25), versus 20% in controls (p = 0.09). CONCLUSION: Thiopurine exposure was associated with a significantly increased risk of ICP among patients with IBD compared to non-exposed IBD patients and age-matched general population controls. The course of ICP was not significantly different in thiopurine-exposed cases.

Is sleep deficit associated with infertility and recurrent pregnancy losses? Results from a prospective cohort study.

INTRODUCTION: Biological rhythms, the innate cycle of changes in the body's physiological functions, are circadian if they have a 24-hour period. It is known that sleep is a key feature of human circadian rhythm but the relation between sleep and female fertility is largely unknown. This paucity of research is surprising given that circadian rhythms are paramount to human physiology and sleep is related to major female reproductive events. This study was designed to investigate whether there is a difference between the sleep and activity parameters of women with poor reproductive outcome compared with healthy, fertile parous women (comparator group) using subjective (questionnaires) and objective (actigraphy and light exposure) measures. MATERIAL AND METHODS: A prospective cohort study in a tertiary in vitro fertilization referral center in the UK; composed of three study groups: women diagnosed with recurrent implantation failure, women with recurrent miscarriage (RM) and a comparison group (fertile women without endometrial pathology). Comparison women were selected gynecology patients without endometrial disease (ie perineal complaints or altruistic egg donors). Primary outcome was differences in objective length of sleep in each of the participant groups using actigraphy. Secondary outcomes were subjective sleep quality and quantity, using participant questionnaires, light exposure, and the feasibility of machine learning in activity-pattern interpretation. RESULTS: Women with recurrent implantation failure slept daily on average for 7 hours 35 minutes (± 57 min), 53 minutes less than the comparison group (P = .03), although quality of their objective sleep, and quantity of their subjective sleep, were not significantly different. Women with recurrent miscarriage slept less that the comparison women (36 minutes less/night) but more than women with recurrent implantation failure (17 minutes more/night). No difference in light exposure was found between recurrent miscarriage and the recurrent implantation failure and comparison groups. CONCLUSIONS: This study demonstrates an objective observation of sleep time reduction in women with subfertility, although it is not yet clear if this association is casual. Given our increased understanding of the internal body clock and circadian rhythm on fertility, our observation warrants further investigation.

Are trainees working in obstetrics and gynecology confident and competent in the care of frail gynecological oncology patients?

INTRODUCTION: Older patients undergoing cancer surgery are at increased risk of post-operative complications, prolonged hospital stay, and mortality. Identification of frailty can help predict patients at high risk of peri-operative complications and allow a collaborative, multidisciplinary team approach to their care. A survey was conducted to assess the confidence and knowledge of trainees in obstetrics and gynecology regarding identification and management of peri-operative issues encountered in frail gynecological oncology patients. METHODS: A web-based survey was distributed via the Audit and Research in Gynaecological Oncology (ARGO) collaborative and UK Audit and Research Collaborative in Obstetrics and Gynaecology (UKARCOG) . The survey on the management of frail peri-operative patients was disseminated to doctors-in-training (trainees) working in obstetrics and gynecology in the United Kingdom (UK) and Ireland. Specialty (ST1-7), subspecialty, and general practice trainees, non-training grade doctors, and foundation year doctors currently working in obstetrics and gynecology were eligible. Consultants were excluded. Study data were collected using REDCAP software hosted at the University of Manchester. Responses were collected over a 6-week period between January and February 2020. RESULTS: Of the 666 trainees who participated, 67% (425/666) reported inadequate training in peri-operative management of frail patients. Validated frailty assessment tools were used by only 9% (59/638) of trainees and less than 1% (4/613) were able to correctly identify all the diagnostic features of frailty. Common misconceptions included the use of chronological age and gender in frailty assessments. The majority of trainees (76.5%, 448/586) correctly answered a series of questions relating to mental capacity; however, only 6% (36/606) were able to correctly identify all three diagnostic features of delirium. A total of 87% (495/571) of trainees supported closer collaboration with geriatricians and a multidisciplinary approach. CONCLUSIONS: Obstetrics and gynecology trainees reported inadequate training in the peri-operative care of frail gynecological oncology patients, and overwhelmingly favored input from geriatricians. Routine use of validated frailty assessment tools may aid diagnosis of frailty in the peri-operative setting. There is an unmet need for formal education in the management of frail surgical patients within the UK and Irish obstetrics and gynecology curriculum.

Identifying stably expressed housekeeping genes in the endometrium of fertile women, women with recurrent implantation failure and recurrent miscarriages.

Housekeeping genes (HKG) are presumed to be constitutively expressed throughout tissue types but recent studies have shown they vary with pathophysiology. Often, validation of appropriate HKG is not made. There is no consensus on which HKGs are most stably expressed in endometrial tissue so this study aimed to identify the most stable HKG in the endometrium of women with recurrent implantation failure (RIF) and recurrent miscarriages (RM). Inclusion criteria were women between 25-45 years (n = 45) suffering recurrent miscarriage (RM), recurrent implantation failure (RIF) or fertile controls. Endometrial biopsies were taken and total RNA extraction, cDNA synthesis and PCR was performed using 10 candidate HKG. The genes were arranged in terms of stability and normalisation was determined. Several HKGs not previously tested in endometrial samples were found to be more stable than those previously identified as the most stable. Of these, the 5 most stable HKG (in order of stability) were Prdm4 (PR domain 4) > Ube4a (Ubiquitin-Conjugating Enzyme 4a) > Enox2 (Ecto-NOX Disulfide-Thiol Exchanger 2) > Ube2d2 (Ubiquitin-conjugating enzyme E2D 2) > Actb (Actin beta). We therefore recommend using at least four of the aforementioned HKG for normalisation of endometrial tissues taken from patients with RM and RIF.

The increasing incidence of foetal echogenic congenital lung malformations: an observational study.

OBJECTIVES: The aim of this study was to investigate the incidence of congenital lung malformations over the past 19 years. Congenital lung malformations (CLM) are a heterogeneous group of lung abnormalities. The antenatal diagnosis is important for foetal and neonatal management but there have been no studies examining whether the reported incidence of this abnormality is constant. METHODS: A retrospective cross-sectional study of cases identified from the Wessex Antenatally Detected Anomalies (WANDA) register 1994-2012. RESULTS: One hundred and thirty-three cases of CLM in 524 372 live and stillbirths were identified. All but seven were identified on antenatal ultrasound. During the early registry (1994-1998) the average incidence of CLM was 1.27 per 10,000 births. By the last 4 years (2008-2012) this had risen to 4.15 per 10,000 births, with a progressive increase during the intervening years. CONCLUSION: There was over a three-fold increase in the antenatally detected CLM in the Wessex region 1994-2012. Comparison with the antenatal detection of diaphragmatic hernia suggests that this is a true rise in incidence rather than an artefactual increase due to increased antenatal recognition secondary to improved ultrasound resolution and operator experience. These results have clinical and cost implications for practitioners of foetal medicine, neonatology and paediatric surgery services.

Influence of shift work on early reproductive outcomes: a systematic review and meta-analysis.

OBJECTIVE: To determine whether an association exists between shift work and early reproductive outcomes. DATA SOURCES: MEDLINE, Embase, and Web of Science were searched. Additional sources included Google Scholar, the Cochrane Library, online publications of national colleges, the ClinicalTrials.gov, and references of retrieved papers. METHODS OF STUDY SELECTION: Included studies compared female shift workers (work outside 8:00 AM to 6:00 PM) with nonshift workers with menstrual disruption (cycles less than 25 days or greater than 31 days), infertility (time-to-pregnancy exceeding 12 months), or early spontaneous pregnancy loss (less than 25 weeks). TABULATION, INTEGRATION, AND RESULTS: Two reviewers extracted adjusted and raw data. Random effect models were used to pool data weighting for the inverse of variance. Assessments of heterogeneity, bias, and subgroup analyses were performed. Sixteen independent cohorts from 15 studies (123,403 women) were subject to analysis. Shift workers had increased rates of menstrual disruption (16.05% [2,207/13,749] compared with 13.05% [7,561/57,932] [n=71.681, odds ratio {OR} 1.22, 95% confidence interval {CI} 1.15-1.29, I 0%]) and infertility (11.3% [529/4,668] compared with 9.9% [2,354/23,811] [OR 1.80, 95% CI 1.01-3.20, I 94%]) but not early spontaneous pregnancy loss (11.84% [939/7,931] compared with 12.11% [1,898/15,673] [n=23,604, OR 0.96, 95% CI 0.88-1.05, I 0%]). Night shifts were associated with increased early spontaneous pregnancy loss (n=13,018, OR 1.29, 95% CI 1.11-1.50, I 0%). Confounder adjustment led to persistent relationships between shift work and menstrual disruption (adjusted OR 1.15, 95% CI 1.01-1.31, I 70%) but not infertility (adjusted OR 1.11 95% CI 0.86-1.44, I 61%). The association between night shifts and early spontaneous pregnancy loss remained (adjusted OR 1.41 95% CI 1.22-1.63, I 0%). CONCLUSION: This review provides evidence for an association between performing shift work and early reproductive outcomes, consistent with later pregnancy findings. However, there is currently insufficient evidence for clinicians to advise restricting shift work in women of reproductive age.

Are skin scar characteristics associated with the degree of pelvic adhesions at laparoscopy?

OBJECTIVE: To investigate whether individual or a combination of abdominal surgical scar characteristics can predict the severity and extent of intra-abdominal adhesions. DESIGN: A prospective cohort study. SETTING: A tertiary referral center in the United Kingdom. PATIENT(S): One hundred women who had previously undergone abdominopelvic surgery and were undergoing an elective laparoscopic gynecologic operations. INTERVENTION(S): Abdominal scars were evaluated preoperatively using the modified Manchester Scar Questionnaire Adhesions were assessed intraoperatively and compared with the cutaneous findings. MAIN OUTCOME MEASURE(S): Presence and severity of intra-abdominal adhesions. RESULT(S): Of 100 women recruited into this study, 71 (71%) women were found to have intra-abdominal Aadhesions, and 29 (29%) had no adhesions. Women who had more than one abdominal scar, a palpable scar, and/or a longer scar were most likely to have pelvic adhesions during the current surgery. Women with the highest mean scar scores also had a greater total adhesion score. CONCLUSION(S): Adhesions are a common postoperative consequence of open or laparoscopic surgery. Skin scar characteristics are associated with the presence and degree of pelvic adhesions. Future studies should examine whether these characteristics can be used as a preoperative predictive tool to facilitate surgical decision-making and elective operating room organization.