Mini-commentary on BJOG-19-1139.R1: Mesh inlay, mesh kit or native tissue repair for women having repeat anterior or posterior prolapse surgery: randomised controlled trial (PROSPECT)

Background: Sub-Saharan African (SSA) countries have high stillbirth rates compared to high-income countries, yet research on risk factors for stillbirth in SSA remain scant. Objectives: To identify the modifiable risk factors of stillbirths in SSA and investigate their strength of association using a systematic review. Search Strategy: EMBASE, MEDLINE, Global Health, and CINAHL Plus databases were searched for literature. Selection Criteria: Observational population- and facility-level studies exploring stillbirth risk factors, published between 2013-2019 were included. Data Collection and Analysis: Narrative synthesis of data was undertaken and the potential risk factors were classified into sub-groups. Main Results: Thirty-seven studies were included, encompassing 20,264 stillbirths. The risk factors were categorized as maternal antepartum (0-4 antenatal care visits, multiple gestations, hypertension, birth interval >3 years, history of perinatal death); socioeconomic factors (maternal lower wealth index and basic education, advanced maternal age, grand multiparity (≥5)); intrapartum (direct obstetric complication, non-vaginal delivery); fetal (low birthweight and gestational age <37weeks) and health systems (poor ANC quality, emergency referrals, ill-equipped facility). The proportion of unexplained stillbirths remained very high. No association was found between stillbirths and HIV, BMI, diabetes, and distance from the facility. Conclusion: The overall quality of evidence was low as many studies were facility-based and did not adjust for confounders. This review identified preventable risk factors for stillbirth. Focused programmatic strategies should be developed to improve antenatal care, emergency obstetric care, maternal perinatal education, referral and outreach systems, and birth attendant training. More population-based high-quality research is needed. Funding: Not externally funded

Mini- commentary on BJOG-19-1190.R1: Cardio-metabolic risk factors among young infertile women: a systematic review and meta-analysis

Background: Normal mature sperm have a considerably reduced number of mitochondria which provide the energy required for progressive sperm motility. Literature suggests that disorders of sperm motility may be linked to abnormal sperm mitochondrial number and function. Objectives: To summarise the evidence from literature regarding the association of mitochondrial DNA copy numbers and semen quality with a particular emphasis on the spermatozoa motility. Search strategy: Standard methodology recommended by Cochrane. Selection criteria: All published primary research reporting on differences in mitochondrial DNA copy numbers between the sperm of males with a normal and abnormal semen analysis. Data collection and analysis: Using standard methodology recommended by Cochrane we pooled results using a random effects model and the findings were reported as a standardised mean difference. Main results: We included 10 trials. The primary outcome was sperm mitochondrial DNA copy numbers. A meta-analysis including five studies showed significantly higher mitochondrial DNA copy numbers in abnormal semen analysis as compared to normal semen analysis(SMD 1.08, 95% CI 0.74-1.43). Three other studies not included in the meta-analysis showed a significant negative correlation between mitochondrial DNA copy numbers and semen parameters. The quality of evidence was assessed as good to very good in 60% of studies. Conclusions: Our review demonstrates significantly higher mitochondrial DNA in human sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis. PROSPERO registration: CRD42019118841 Funding None received

Endometriosis is a common health condition affecting women of reproductive age who often present with chronic pelvic pain and/or infertility. There is wide variation in the estimates of endometriosis prevalence. Accurate reporting of the disease prevalence is hampered by multiple factors including long delay in diagnosis due to natural fluctuation in symptoms severity, lack of a reliable non-surgical diagnostic tool, polymorphic appearance of endometriosis lesions at laparoscopy, inability to achieve histological confirmation is all suspected cases and tendency for disease recurrence. Therefore, a longitudinal, rather than cross-sectional, cohort study design spanning an extended follow-up period is better suited to assess endometriosis prevalence. In this issue of BJOG, Rowlands and colleagues (2020) linked longitudinal survey data to three administrative health databases to identify the prevalence of endometriosis among 13,508 young Australian women followed up for nearly 20 years. The study reported a 6% cumulative prevalence of clinically-confirmed endometriosis and an additional 5.4% of clinically-suspected endometriosis. If these figures reflect the true prevalence of endometriosis, then one in nine women will be diagnosed with endometriosis at some point during their reproductive years up to the age of 44 with a peak at 30-34 years, thus underscoring the significant impact of the disease on the well-being and quality of life in young women and the enormous burden on healthcare resources needed to diagnose and treat endometriosis and its sequelae.The data presented in the study of Rowlands and colleagues (BJOG 2020) included patients who could have been diagnosed with adenomyosis but their condition was coded as endometriosis. This is unlikely to have significantly over-estimated the prevalence of endometriosis as recent evidence suggests adenomyosis prevalence to be only 1% with a considerable proportion of those patients having co-existing endometriosis (Yu et al, Am J Obstet Gynecol 2020; 223: 94.e1-10). The same can not be said about the 5.4% of clinically-suspected endometriosis cases. Symptoms review, clinical examination and various imaging modalities, including ultrasound scanning and magnetic resonance imaging, represent the cornerstone of non-invasive diagnosis of endometriosis. Current evidence suggests that the predictive accuracy of those non-invasive methods in the diagnosis of endometriosis compared to laparoscopy and histological confirmation is modest (Nisenblat et al, Cochrane Database Syst Rev, 2016 (2): CD009591) and depends on the combination of diagnostic tools used as well as the site and extent of the endometriosis lesions (Reid et al, Eur J Obstet Gynecol Reprod Biol 2019; 234: 171-178). These data are not provided in the study of Rowlands and colleagues. It is therefore difficult to accurately estimate the prevalence of endometriosis whether it’s the 6% clinically-confirmed rate or the full 11.4% confirmed and suspected rate. The truth probably lies somewhere in the middle! Future epidemiological studies should endeavour to elucidate on the distinction between the different methods used in the diagnosis of endometriosis with reference to the predictive accuracy of each diagnostic modality to help advance our understanding of the incidence and risk factors associated with this debilitating gynaecological condition.Mr. Tarek A El-ToukhyAssisted Conception Unit, Guys and St. Thomas Hospital NHS Trust11th Floor, Tower Wing,Guys Hospital,St. Thomas Street tarekeltoukhy@hotmail.com

Dear Editor, We would like to thank Dr. Lamont and colleagues for their interesting commentary.1 The authors point out very pressing topics that deserve more attention than we could provide in the original manuscript.They expressed concerns in their letter towards the heterogeneity of the data that were used in our meta-analysis. If incidences differ between regions and populations, absolute numbers on colonisation and neonatal infections might not be comparable. However, new policies were implemented in various settings, where differences in outcomes were measured under the same local circumstances. So as rightly mentioned by Lamont et al, data from the US cannot and should not be used as a blueprint for other parts of the world.1 Yet the general trend in developed countries that we observed, might shed some new light on the respective effectiveness of the strategies currently available.

Mini-commentary on BJOG-20-1239.R3: Intramuscular oxytocin versus Syntometrine versus carbetocin for prevention of primary postpartum haemorrhage after vaginal birth: a randomised double blinded clinical trial of effectiveness, side effects and quality of life

BJOG-20-2353.R2 What should we believe when systematic reviews disagree?For many years, uterine balloon tamponade (UBT) has been used to treat severe postpartum haemorrhage (PPH), despite a lack of randomised trials to demonstrate its effectiveness. With commercial devices being expensive, clinicians in low resource settings have made their own using 2 low-cost, widely available items (Foley catheters and condoms). Public health experts have been so confident of their benefit that large programmes have been set up to disseminate the necessary skills worldwide.Recently, however, the global maternal health community has been thrown into disarray when not one, but two randomised controlled efficacy trials suggested that outcomes with condom catheter UBTs were actuallyworse than normal care in low resource settings. The Cochrane meta-analysis concluded that “in [low resource] settings, balloon tamponade [should be] only introduced alongside multi‐system improvements in PPH care” (Kellie et al. Cochrane Database of Systematic Reviews 2020(7): CD013663).Systematic reviews may be the pinnacle of evidence-based medicine, but even they can differ in how to interpret evidence. And so, proponents of the condom catheter conducted their own systematic review with far wider inclusion criteria – they not only included the randomised trials but examined success rates from 15 non-randomised trials and 69 case series (Suarez et al. Am J Obstet Gynecol 2020;222(4):293.e1–e52). Furthermore, the primary outcome was the success rate of the technique (overall 86%) rather than the risk of morbidity and mortality compared to controls, as used in the Cochrane review. This is problematic, as reported ‘success rates’ without controls can be very difficult to interpret: in initial case series misoprostol showed similar success rates against life-threatening haemorrhage before RCTs eventually showed it to be less effective than oxytocin.A third version of the same review is published today by a WHO team (Pingray et al. BJOG 2021;XXX,XXX). This time they include only 4 high quality studies in which UBT was compared to standard care. With a composite maternal morbidity / mortality outcome, they found no evidence of benefit and concluded that “the effect … is unclear, as is the role of the type of device and the setting”. WHO studies are now underway to address this uncertainty.But why is this all so important? The difficulty comes because the World Health Organisation has been updating its guidance on PPH management, and had to declare a position on UBT. The recently-published guideline, drawn up by independent experts, accepts the validity of the RCTs but recognises that there is wide acceptability of the technique and that the evidence of harm is only for condom catheters and onlyin resource-poor settings. They put a high emphasis on minimising harm and conclude that UBTs should only be used in settings where there is already a good standard of care, including recourse to blood transfusion and surgery if needed (WHO. Geneva: World Health Organization; 2021).Until further studies are published, the debate will continue. But this episode shows how the choice of inclusion criteria and outcomes in systematic reviews are critical, both for their conclusions, and for global policy.

Letter to the Editor, BJOG Exchange

Objective: To determine the peri-operative characteristics associated with an increased risk of post-operative urinary retention (POUR) following vaginal pelvic floor surgery. Design: A retrospective cohort study using multivariable prediction modelling. Setting: A tertiary referral urogynaecology unit. Population: Patients undergoing vaginal pelvic floor surgery from January 2015 to February 2020. Methods: Eighteen variables (24 parameters) were compared between those with and without POUR and then included as potential predictors in statistical models to predict POUR. The final model was chosen as the one with the largest c-index from internal cross-validation. This was then externally validated using a separate data set (n=94) from another surgical centre. Main Outcome Measures: diagnosis of POUR following surgery while the patient was in hospital. Results: Among the 700 women undergoing surgery, 301 (43%) experienced POUR. Pre-operative variables with statistically significant univariate relationships with POUR included age, menopausal status, prolapse stage, and uroflow parameters. Significant peri-operative factors included estimated blood loss, amount of intravenous fluid administered, operative time, length of stay, and specific procedures including vaginal hysterectomy with intraperitoneal vault suspension, anterior colporrhaphy, posterior colporrhaphy, and colpocleisis. The lasso logistic regression model had the best combination of internally cross-validated c-index (0.73) and accurate calibration curve. Using this data, a POUR risk calculator was developed (https://pourrisk.shinyapps.io/POUR/). Conclusions: This POUR risk calculator will allow physicians to counsel patients pre-operatively on their risk of developing POUR after vaginal pelvic surgery and help focus discussion around potential management options.

Objectives: Assess first trimester serum placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFLT-1), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), endothelin and vascular cell adhesion molecule (VCAM) in women with chronic hypertension (CH) stratified according to blood pressure (BP) control. Design: Case-control. Setting: Tertiary referral centre. Population: 650 women with CH, 142 normotensive controls. Methods: In the first trimester, patients with CH were subdivided into 4 groups. Group 1 included women without pre-pregnancy CH presenting with BP ≥140/90mmHg. Groups 2-4 had pre-pregnancy CH; in group 2 the BP was <140/90mmHg without antihypertensive medication, in group 3 the BP was <140/90mmHg with antihypertensive medication and in group 4 the BP was ≥ 140/90 mmHg despite antihypertensive medication. PLGF, sFLT-1, IL-6, TNF-α, endothelin and VCAM were measured at 11+0-13+6 weeks’ and converted into multiples of the expected median (MoM) using multivariate regression analysis in the controls. Main outcome measure: Comparisons of MoM values of PLGF, sFLT-1, IL-6, TNF-α, endothelin and VCAM between the 4 CH groups and the controls were made using analysis of variance or Kruskal-Wallis tests. Results: In the CH groups, compared to controls, PLGF was reduced in groups 2-4, sFLT-1 was reduced in groups 2 and 3, endothelin was increased in groups 1 and 4 but IL-6 was reduced in group 4. Conclusion: In women with CH, differences exist in first trimester angiogenic and inflammatory profiles according to BP control. Further evaluation is needed to determine if these differences are useful in the stratification of care.

A document by Birgit Arabin. Click on the document to view its contents.

Objective: Approximately 50% women who give birth after Obstetric Anal Sphincter Injury (OASI) develop anal incontinence (AI) over their lifetime. We review current evidence for protective benefit of planned cesarean section (CS) to prevent AI after OASI. Design and setting: Systematic review and meta-analysis according to prospectively published methodology. Population and methods: All studies reporting outcomes after an OASI and subsequent birth by any mode. Main outcome measures: AI measurement after OASI and subsequent birth. Total AI, new/worsening AI, quality of life, satisfaction, regret. Results: 86 of 2472 screened studies met inclusion criteria. All studies contributing to meta-analyses were at high risk of bias. There was no evidence of difference in new or worsening AI after subsequent vaginal birth (VB) compared to subsequent CS after OASI across all time periods (p=0.53: CI 0.72-1.19; 9 studies, 2104 participants); ≤2y (p=0.83: CI 0.65-1.72; 7 studies, 569 participants) or ≥5y after subsequent birth (p=0.39: CI 0.65-1.18; 2 studies; 1535 participants). There was no difference between subsequent CS or VB in asymptomatic women or for other AI or QOL outcomes. There was no evidence of difference in AI in women who subsequently delivered vs those who did not (p=0.9: CI 0.71-1.34; 10 studies, 970 participants); or pre- subsequent birth vs post-subsequent birth (p=0.31; CI 0.51-1.25, 13 studies, 5496 participants). Conclusions: Due to evidence quality (majority non-randomised studies) we are unable to determine whether planned cesarean is protective against AI after OASI. Higher quality data is required to guide practice in this area, specifically in asymptomatic women and for long-term outcomes.

Objective: To evaluate objective and subjective outcomes of patients who underwent sacrocolpopexy using autologous rectus fascia to provide more data regarding non-mesh alternatives in pelvic organ prolapse surgery. Design: Cohort study with retrospective and prospective data. Setting: A single academic medical center. Population: Women who underwent abdominal sacrocolpopexy using autologous rectus fascia between January 2010 and December 2019 Methods: Patients were recruited for a follow-up visit including completing the Pelvic Floor Distress Inventory (PFDI) and Pelvic Organ Prolapse Quantification (POPQ) exam. Demographic and clinical characteristics were collected. Main Outcome Measures: Composite failure, anatomic failure, symptomatic failure, and retreatment. Results: During the study period, 132 women underwent sacrocolpopexy using autologous rectus fascia. Median follow-up time was 2.2 years. Survival analysis showed that composite failure was 0.8% (CI 0.1-5.9%) at 12 months, 3.5% (CI 1.1-10.7%) at 2 years, 13.2% (CI 7.0-24.3%) at 3 years, and 28.3% (CI 17.0-44.8%) at 5 years. Anatomic failure was 0% at 12 months, 1.4% (CI 0.2-9.2%) at 2 years, 3.1% (CI 0.8-12.0%) at 3 years, and 6.8% (CI 2.0-22.0%) at 5 years. Symptomatic failure rate was 0% at 12 months, 1.3% (CI 0.2-9.0%) at 2 years, 2.9% (CI 0.7-11.3%) at 3 years, and 13.1% (CI 5.3-30.3%) at 5 years. Retreatment rate was 0.8% (CI 0.1-5.9%) at 12 months and 2 years, 9.4% (CI 4.2-20.3%) at 3 years, and 13.0% (CI 6.0-27.2%) at 5 years. Conclusions: Autologous rectus fascia sacrocolpopexy may be considered a safe and effective alternative for patients who desire to avoid synthetic mesh.

Mini-commentary on BJOG-19-1876.R1: Glycosylated fibronectin point-of-care test for diagnosis of preeclampsia in a low-resource setting: a prospective Southeast Asian population study

A document by Jan Deprest. Click on the document to view its contents.

Objectives: To investigate psychological correlates in women referred with suspected ovarian cancer via the fast-track pathway, explore how anxiety and distress levels change 12 months post-testing and report cancer conversion rates by age and referral pathway. Design: Single arm prospective cohort study Setting: Multicentre. Secondary care including outpatient clinics and emergency admissions. Participants: 2596 newly presenting symptomatic women with a raised CA125 level, abnormal imaging or both. Methods: Women completed anxiety and distress questionnaires at recruitment and at 12 months for those who had not undergone surgery or a biopsy within 3 months of recruitment. Main outcome measures: Anxiety and distress levels measured using STAI-6 and IES-r questionnaires. OC conversion rates by age, menopausal status and referral pathway. Results: 1355/2596 (52.1%) and 1781/2596 (68.6%) experienced moderate-to-severe distress and anxiety at recruitment. Younger age and emergency presentations had higher distress levels. Clinical category for anxiety and distress remained unchanged/worsened in 76% at 12 months despite a non-cancer diagnosis. OC rates by age were 1.6% (95% CI 0.5 to 5.9) under 40 and 10.9 % (95% CI 8.7 to 13.6) over 40 years. In women referred through fast-track pathways, 3.3% (95% CI 1.9 to 5.7) of pre- and 18.5% (95% CI 16.1 to 21.0) of postmenopausal women were diagnosed with OC. Conclusions: Women undergoing diagnostic testing display severe anxiety and distress. Younger women are especially vulnerable and should be targeted for support. Women under 40 have low conversion rates and we advocate reducing testing in this group to reduce harms of testing.

Mini-commentary on BJOG-19-1550.R1: Effect of Progestogen for Women with Threatened Miscarriage: A Systematic Review and Meta-analysis