Subclinical hypothyroidism and antithyroid autoantibodies in women with subfertility or recurrent pregnancy loss: Scientific Impact Paper No. 70 June 2022: Scientific Impact Paper No. 70 June 2022.

The thyroid is a gland located in the neck and is important for many processes in the body. Problems with the thyroid gland are common in women of reproductive age. It is essential to have a normal working thyroid gland in order to achieve a successful pregnancy. One of the most common problems with the thyroid is underactivity (known as hypothyroidism). An early, mild form of an underactive thyroid is called subclinical hypothyroidism. Often people with this condition do not have any symptoms. Another common problem is thyroid autoimmunity. Here, the immune system attacks the thyroid gland, sometimes leading to the development of abnormal thyroid function. This can be diagnosed by the presence of proteins in the bloodstream called antibodies. Mild thyroid problems and the presence of high levels of thyroid antibodies have been linked to miscarriage and premature birth. There is debate in medicine about whether there should be routine testing of thyroid function both in the general population and in individuals who are trying for a baby. In addition, the strategies used to manage certain thyroid problems are questioned. Discussions around testing and subsequent management particularly relate to women with a history of subfertility or repeated miscarriages. This Scientific Impact Paper provides information on thyroid testing and the management of mild thyroid problems and thyroid antibodies in women with a history of subfertility or recurrent miscarriages, using the latest evidence and guidelines. It concludes that there may be a role for treating these women with thyroxine tablets (the hormone produced by the thyroid gland) when subclinical hypothyroidism is present, and gives guidance on the cut-off levels for treatment.

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone. METHODS: MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 µg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m2vs ≥35 kg/m2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024. FINDINGS: Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups. INTERPRETATION: Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Predicting Postpartum Hemorrhage (PPH) during Cesarean Delivery Using the Leicester PPH Predict Tool: A Retrospective Cohort Study.

OBJECTIVE: The aim of the present study was to develop a toolkit combining various risk factors to predict the risk of developing a postpartum hemorrhage (PPH) during a cesarean delivery. STUDY DESIGN: A retrospective cohort study of 24,230 women who had cesarean delivery between January 2003 and December 2013 at a tertiary care teaching hospital within the United Kingdom serving a multiethnic population. Data were extracted from hospital databases, and risk factors for PPH were identified. Hothorn et al recursive partitioning algorithm was used to infer a conditional decision tree. For each of the identified combinations of risk factors, two probabilities were calculated: the probability of a patient producing ≥1,000 and ≥ 2,000 mL blood loss. RESULTS: The Leicester PPH predict score was then tested on the randomly selected remaining 25% (n = 6,095) of the data for internal validity. Reliability testing showed an intraclass correlation of 0.98 and mean absolute error of 239.8 mL with the actual outcome. CONCLUSION: The proposed toolkit enables clinicians to predict the risk of postpartum hemorrhage. As a result, preventative measures for postpartum hemorrhage could be undertaken. Further external validation of the current toolkit is required.

Raising quality whilst reducing cost in health care: A retrospective cohort study.

OBJECTIVE: The objective of this study was to investigate the relationship between cost and quality within the health care sector and to establish which factors could influence this relationship. The aim was to investigate the dynamics of the relationship, in order to improve the quality whilst reducing the cost. DESIGN: This is a retrospective cohort study, analysing quality, safety, and financial data from a 5-year period. SETTING: A publicly funded tertiary hospital. PARTICIPANTS: The dependent variable was cost saved, and the independent variables were patient safety, patient satisfaction, and clinical efficiency. MAIN OUTCOME MEASURES: Financial savings and quality domains. RESULTS: A statistically significant relationship between the variables was found. Multivariate analysis derived the equation Y = ßX1  + c, where Y is the cost saved, ß is the beta coefficient, X1 is the clinical efficiency, and c is a constant. R2 = 0.874 (coefficient of determination), which suggested that the cost saved by the unit varied due to clinical efficiency. Clinical efficiency accounted for 87.4% of the variation in the cost saved by the unit. CONCLUSIONS: The results indicated that, after the trade-off value, an improvement in the quality would result in reduced costs for the unit. Clinical efficiency of the services was found to be the key factor determining this relationship. Therefore, strategies to increase clinical efficiency, and thus overall quality, above the trade-off level could result in significant financial savings. Patient safety and patient experience were positively correlated with clinical efficiency.

Work-related musculoskeletal injuries amongst obstetrics and gynaecology trainees in East Midland region of the UK.

PURPOSE: Work-related musculoskeletal injuries (WRMSI) have been well known amongst obstetrics and gynaecology (O&G) practitioners, but limited data have been reported. Our aim is to determine the prevalence, severity and characteristics of WRMSI amongst O&G trainees. METHODS: A musculoskeletal ergonomic survey was conducted amongst the O&G trainees in the East-Midlands region of United Kingdom (UK). The survey comprised of demographic details, year of training, previous manual handling training, any work-related orthopaedic injury, the type of injury, any treatment received in addition to any sick leave incurred after the injury were also documented. RESULTS: The response rate for the survey was 76% (59/78). The majority (22%) were senior specialist trainee, seventh year (ST7) and between 30 and 34 age groups. Approximately 90% of the trainees reported to have experienced pain in the last year. The most common site was the back, which was followed by the shoulders and the upper limbs. 63% of trainees reported injuries that were attributed to WRMSI. One in ten of the trainees needed time off work due to injury. A total of 20 days were lost in the last 12 months as a result of pain or discomfort attributed to obstetric work. CONCLUSIONS: Our results demonstrate the prevalence of work-related injuries and its detrimental effects. Such injuries are underreported on incident reporting system. Ergonomics and WRMSI prevention in obstetrics and gynaecology is an area seldom discussed. Obstetric training sessions should incorporate ergonomic interventions. Further research is required to establish relevant aetiological factors related to WRMSI in this specialty.

Knowledge of human papillomavirus and the human papillomavirus vaccine in European adolescents: a systematic review.

BACKGROUND: The human papillomavirus (HPV) vaccine is recommended for adolescent girls in many European countries, however there is huge variation in vaccine uptake. METHODS: A mixed methods systematic review to ascertain the level of HPV and HPV vaccine knowledge that exists among European adolescents. Two electronic databases, Ovid Medline and PsychInfo, were searched from origin to September 2014. Meta-analysis was performed for the two primary outcome measures ('have you heard of HPV?' and 'have you heard of the HPV vaccine?'), assessing for the correlation between gender and knowledge. This was supplemented with meta-synthesis for the remaining associations and secondary outcomes. RESULTS: 18 papers were included in the final review. Overall European adolescents had poor understanding of basic HPV and HPV vaccine knowledge. Meta-analysis identified that female adolescents are more likely to have heard of HPV (n=2598/5028 girls versus n=1033/3464 boys; OR 2.73, 95% CI 1.86-3.99) and the HPV vaccine (n=1154/2556 girls versus n=392/2074 boys; OR 5.64, 95% CI 2.43-13.07), compared to males. Age, higher education and a positive vaccination status were also associated with increased awareness. There was limited appreciation of more detailed HPV knowledge and uncertainty existed regarding the level of protection offered by the vaccine and the need for cervical screening post vaccination. CONCLUSIONS: The delivery of HPV education to European adolescents needs to be re-evaluated, since at present there appears to be significant deficiencies in their basic knowledge and understanding of the subject. Increasing HPV knowledge will empower adolescents to make informed choices regarding participation with HPV related cancer prevention health strategies.

Experiences and emotional strain of NHS frontline workers during the peak of the COVID-19 pandemic.

BACKGROUND: The mental health of the population has been negatively affected due to the pandemic. Frontline healthcare workers with increased exposure to COVID diagnosis, treatment and care were especially likely to report psychological burden, fear, anxiety and depression. AIM: To elicit how working as a health professional during the pandemic is impacting on the psychological wellbeing of frontline staff. METHOD: United Kingdom population of healthcare workers were approached by advertising the survey via social media, NHS trusts and other organisations. Open-ended survey answers were qualitatively explored using content analysis. RESULTS: Survey collected data from 395 NHS staff was developed into three themes; (1) Despair and uncertainty: feeling overwhelmed trying to protect everyone, (2) Behavioural and psychological impact: affecting wellbeing and functioning and (3) Coping and employer support: getting the right help. CONCLUSION: NHS staff felt enormous burden to adequately complete their professional, personal and civil responsibility to keep everyone safe leading to negative psychological and behavioural consequences and desire for NHS employers to offer better support. As the pandemic progresses, the results of this study may inform NHS employers on how optimum support can be offered to help them cope with negative psychological consequences of the pandemic.

Management of recurrent implantation failure: British Fertility Society policy and practice guideline.

Recurrent implantation failure (RIF) is defined as the absence of a positive pregnancy test after three consecutive transfers of good quality embryos. There remains significant variation in clinical practice in the management of RIF. This British Fertility Society (BFS) Policy and Practice guideline analyses the evidence for investigations and therapies that are employed in RIF and provides recommendations for clinical practice and for further research. Evidence for investigations of sperm and egg quality, uterine and adnexal factors, immunological factors and thrombophilia, endocrine conditions and genetic factors and for associated therapies have been evaluated. This guideline has been devised to assist reproductive medicine specialists and patients in making shared decisions concerning management of RIF. Finally, suggestions for research towards improving understanding and management of RIF have also been provided.

Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: the MifeMiso RCT.

TRIAL DESIGN: A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne®, Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage. METHODS: Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1 : 1 ratio) to receive 200 mg of oral mifepristone or matched placebo, followed by 800 µg of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage. RESULTS: A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98; p = 0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94; p = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of £182 (95% confidence interval £26 to £338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone. LIMITATIONS: The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage. FUTURE WORK: Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage. CONCLUSIONS: Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17405024. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 68. See the NIHR Journals Library website for further project information.

Miscarriage is a common complication of pregnancy, affecting approximately one in four women. Sometimes, medical treatment (i.e. tablets) may be offered to start or speed up the miscarriage process in order for the womb to empty itself. A drug called misoprostol (a tablet that makes the womb contract) is currently recommended for this treatment. However, the addition of another drug called mifepristone [a tablet that reduces pregnancy hormones (Mifegyne^®, Exelgyn, Paris, France)] might help the miscarriage to resolve more quickly. Therefore, we carried out the MifeMiso trial to test if mifepristone plus misoprostol is more effective than misoprostol alone in resolving miscarriage within 7 days. Women were randomly allocated by a computer to receive either mifepristone or placebo, followed by misoprostol 2 days later. Neither the women nor their health-care professionals knew which treatment they received. Some women also talked to the researchers about their experiences of taking part in the study. In total, 711 women were randomised to receive either mifepristone plus misoprostol or placebo plus misoprostol. Overall, 83% of women who received mifepristone plus misoprostol had miscarriage resolution within 7 days, compared with 76% of the women who received a placebo plus misoprostol. Surgery was required less often in women who received mifepristone plus misoprostol: 17% of women who received it required surgery, compared with 25% of women who received the placebo. Treatment with mifepristone did not appear to have any negative effects. Treatment with mifepristone plus misoprostol was more cost-effective than misoprostol alone, with an average saving of £182 per woman. Having taken part in the study, most women would choose medical management again and would recommend it to someone they knew who was experiencing a miscarriage.