A document by Shashikant Sholapurkar. Click on the document to view its contents.

Background Guidelines standardise high-quality evidence-based management strategies for clinicians. Uterine fibroids are a highly prevalent condition and may exert significant morbidity. Objectives The purpose of this study was to appraise national and international uterine fibroid guidelines using the validated AGREE-II instrument. Selection Strategy An electronic database search of PubMed and EMBASE from inception to October 2020 for all published English-language uterine fibroid clinical practice guidelines was undertaken. Data Collection and Analysis 939 abstracts were screened for eligibility by two reviewers independently. Three reviewers used the AGREE-II instrument to assess guideline quality in six domains (scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability, and editorial independence). Recommendations were mapped to allow a narrative synthesis regarding areas of consensus and disagreement. Main Results Eight national (AAGL, SOGC 2014, ACOG, ACR, SOGC 2019, CNGOF, ASRM, and SOGC 2015) and one international guideline (RANZOG) were appraised. The highest scoring guideline was RANZOG 2001(score 56.5%). None of the guidelines met the a priori criteria for being high-quality overall (score >= 66%). There were 166 recommendations across guidelines. There were several areas of disagreement and uncertainty. Conclusions There is a need for high-quality fibroid guidelines given heterogeneity across individuals and a large range of treatment modalities available. There are also areas of controversy in the management of fibroids (e.g. Ulipristal acetate, power morcellation) which also should be addressed in any guidelines. Future guidelines should be methodologically robust to allow high-quality decision-making regarding fibroid treatments.

Mini Commentary – BJOG

Anaemia in pregnancy remains a global health problem In this issue of BJOG Hull et al …… et al report on an important study from South Africa regarding anaemia in pregnancy and the response to iron therapy. They report that in HIV-positive women the response was slower than in HIV-negative women. The underlying causes of anaemia varied and included iron deficiency (as assessed by ferritin levels) as well as concurrent infections (urinary tract infections and tuberculosis)Anaemia in pregnancy (blood haemoglobin Hb<11.0g/dl) occurs in > 40% of women living in low- and middle-income countries (LMIC) and in some settings in Asia prevalence is >60%. (McCauley et al, BMJ Global Health, 2018; 3(3):e000625) The latest WHO recommendations on antenatal care consider anaemia as the world’s second leading cause of disability and one of the most serious global public health problems (WHO Geneva 2016 ) .Although globally the focus has largely been on anaemia in pregnancy resulting from either iron deficiency or malaria, this is an incomplete approach at best. Iron deficiency is hard to measure and confirm as; i) this requires a functioning laboratory to be in place, ii) indicators for iron deficiency are influenced by the presence of concurrent infection, or, iii) repeated measures of Hb are needed to check whether the anaemia is responsive to treatment with iron. By contrast, malaria is relatively easy to diagnose via rapid diagnostic tests or microscopic examination of a stained blood smear slide. The handful of studies which have comprehensively assessed aetiology of anaemia in pregnant women demonstrate that anaemia is most commonly the result of complex multiple underlying factors including nutritional deficiencies as well as infectious diseases. Both nutritional deficiency and other infections (malaria, tuberculosis) are more likely with HIV-infection which itself can lead to anaemia probably through direct suppression of erythropoiesis.Hull et al show what was possible in a real-life clinical practice setting. This example of integration of research into clinical practice is laudable and is illustrative of how such integration could result in better services being made available for women in LMIC where burden of disease is high, but diagnostic tests are largely unavailable. It is sobering to realise that the majority of women world-wide will still only be screened for anaemia during pregnancy using ‘conjunctival inspection’ which is highly inaccurate. (van den Broek et al. Bull WHO 1999; 77(1):15-21) Rapid diagnostic tests are available for Hb, malaria, syphilis, HIV and, more recently, for tuberculosis. We are doing women a dis-service if we cannot offer at least these basic diagnostic tests as part of antenatal care.To prevent anaemia during pregnancy, the ‘fall-back’ position is to offer all women daily iron prophylaxis (30-60mg elemental iron) - with luck tablets are available that include folic acid (0.4mg) - along with presumptive treatment of malaria (various regimes) in endemic areas. Multi-micronutrients (including the required amount of iron and folic acid) might actually be better but cannot be recommended because of lack of evidence and they are still three times as expensive as iron and folic acid supplementation alone (3$ vs 1$ approximately).WHO recently recommended a better understanding of the aetiology of anaemia. A search on PubMed shows a clear lack of papers on the topic and more good research is needed. Investment in the antenatal care package offered to women is also much needed if we are aiming for a global ‘Health for All’.

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

A document by David Savitz. Click on the document to view its contents.

Episiotomy and operative vaginal delivery- Do we need more evidence?A.H. Sultan- Urogynaecology and Pelvic Floor Reconstruction Unit, Croydon University Hospital, London Road, Croydon CR7 7YE- Honorary Reader, St George’s University of LondonEmail:asultan29@gmail.comTel: 00 44 7961386840(ORCID 0000-0001-8979-2304)J.W. de Leeuw, Department of Obstetrics and Gynaecology, Ikazia Ziekenhuis, Rotterdam, the Netherlands(ORCID 0000-0001-5028-8055)DISCLOSURE of INTERESTAbdul Sultan is the co-director of the Croydon Perineal and Anal Sphincter Trauma courses (www.perineum.net)Operative vaginal delivery (OVD) is recognised as a major risk factor in the occurrence of obstetric anal sphincter injuries (OASIs), particularly during first vaginal deliveries. Randomised controlled trials (RCTs) have shown the merits of adopting a policy of restrictive mediolateral episiotomy during normal vaginal delivery, although no RCT to date has included measurements of the angle or size of the episiotomy. The benefits of episiotomy performed during OVD demonstrated in large observational studies are overwhelming (Sultan et al. Eur J Obstet Gynecol Reprod Biol. 2019;240:192-196) .Ankarcrona et al have added another study to this collection and have confirmed the results of most such publications. In their study, based on 11 years of data from the Swedish Medical Birth Register, they have emulated a RCT using propensity scores. Ultimately, both methods used showed an almost identical risk reducing effect as the commonly used logistic regression analysis. demonstrating a significant reduction in OASIs during vacuum extraction associated with the use of mediolateral or lateral episiotomies. The Number Needed to Treat to prevent one OASI was 27, which is known to be fourfold lower in forceps delivery.Is the episiotomy a treatment for a certain condition or disease? In reality, episiotomy is an intervention to reduce the risk for an unwanted side effect of birth. Consequently, the impact is one of risk modification as opposed to treatment. Similar to the study by Ankarcrona et al risk factors are commonly established with the use of observational studies (RCOG Greentop guideline No 29, 2015) . In the last decade, several large observational studies Involving more than 2 million women showed a significantly lower rate of OASI in nulliparous women undergoing OVD with an episiotomy.Given the availability of such studies, based on registered databases, showing significantly lower OASI rates, is there still a need for further evidence? Ankarcrona et al acknowledge Lund et al who have shown in their systematic review that there is an association between the risk reduction for OASI with episiotomy rates; the greatest reduction was shown in studies with episiotomy rates over 70%.Obstetricians opposing the use of routine episiotomy during OVD highlight the lack of a definitive RCT. RCT’s are commonly used to address the treatment effect of an intervention on a particular condition with a well described outcome. However, RCT’s of episiotomy during OVD have proven to be very difficult and usually compare no more than the liberal versus the restricted use of episiotomy. As Ankarcrona et al mention, there is only one pilot RCT of IVD and episiotomy indicating that 1600 OVD will need to be included for a definitive study. However, we believe that the design of such a study should be two separate arms for forceps and vacuum delivery as the inherent risks with/without an episiotomy is different. Such a study with vacuum extraction is currently underway in Sweden.The challenge now is to identify prior to labour which women are at high risk of sustaining OASIS using prediction models based on the pre-existing large national databases.

Letter to the Editor, BJOG Title:Deceleration Area and Deceleration Capacity: Promising predictors of fetal acidaemia in human labour? Visual versus computerised cardiotocographyRe: Georgieva A, Lear CA, Westgate JA, Kasai M, Miyagi E, Ikeda T, Gunn AJ, Bennet L. Deceleration area and capacity during labour-like umbilical cord occlusions identify evolving hypotension: a controlled study in fetal sheep. BJOG 2021; https://doi.org/10.1111/1471-0528.16638.Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKEmail:s.sholapurkar@nhs.net; s.sholapurkar172@gmail.com; Tel: 07906620662Short Running Title: Deceleration area and capacity in labourWord count: 500Corresponding Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKStatement of interest: The author has no conflict of interest or funding to declare.

Background: Pharmacological pain management options can relieve women’s pain during labour and birth. Trials of these interventions have used a wide variety of outcomes, complicating meaningful comparisons of their effects. Consensus about key outcomes would facilitate the development of a core outcome set to assess the effectiveness of labour pain management. Objective: To identify all outcomes used in studies of pharmacological pain management interventions during labour and birth. Design: A review of systematic reviews and their included randomised controlled trials was undertaken. Search Strategy: Cochrane CENTRAL was searched to identify all Cochrane systematic reviews describing pharmacological pain management options for labour and birth. Search terms included “pain management”, “labour” and variants, with no limits on year of publication or language. Selection Criteria: Cochrane reviews and randomised controlled trials contained within these reviews were included, provided they compared a pharmacological intervention with other pain management options, placebo or no treatment. Data Collection and Analysis: All outcomes reported by reviews or trials were extracted and tabulated, with frequencies of individual outcomes reported. Main Results: Nine Cochrane reviews and 227 unique trials were included. In total, 148 unique outcomes were identified and categorised into maternal, fetal, neonatal, child, health service, provider’s perspective, or economic outcome domains. Conclusions: Outcomes of pharmacological pain management interventions during labour and birth vary widely between trials. The standardisation of trial outcomes would permit more meaningful comparison between studies. Funding: No external funding was provided. Keywords: Labour and birth; pain management; pharmacological interventions; systematic review

Objective: To assess the incidence of serious complications and reoperations for recurrence after pelvic organ prolapse (POP) surgery and compare the three most common types of repair. Design: Prospective cohort study using a registry. Setting: 19 surgical centres in France. Population: 2309 women participated between 2017 and 2019. Methods: a multivariate analysis including an inverse probability of treatment weighting approach was used to obtain three comparable groups. Main outcome measures: Serious complications and subsequent reoperations for POP recurrence Results: Mean follow-up was 16.6 months. Surgeries included in the analysis were native tissue vaginal repair (N=504), transvaginal mesh placement (692), and laparoscopic sacropexy with mesh (1113). Serious complications occurred among 52 women (2.3%), and reoperation for recurrence was required for 32 (1.4%). At one year, the cumulative weighted incidence of serious complications was 1.8% for native tissue vaginal repair (95% confidence interval 0-3.9), 3.9% for transvaginal mesh (2.0-5.9), and 2.2% for sacropexy (1.1-2.6). Compared with the native tissue vaginal repair group, the risk of serious complications was higher in the transvaginal mesh group (weighted-HR 3.84, 2.43-6.08), and the sacropexy group (2.48, 1.45-4.23), while the risk of reoperation for prolapse recurrence was reduced in both groups (transvaginal mesh [0.22, 0.13-0.39] and sacropexy [0.29, 0.18-0.47]). Conclusions: Laparoscopic sacropexy with mesh appears to have a better risk profile (few serious complications and few reoperations for recurrence) than transvaginal mesh placement (more serious complications) and native tissue vaginal repair (more reoperations for recurrence). These results are useful for informing women and for shared decision making.

Objective: To assess the general population’s knowledge regarding the utility and availability of tools to diagnosis endometriosis, with focus on ultrasound. Design: An international cross-sectional online survey study was performed between August and October 2019. Setting and Population: 5301 respondents, representing 73 countries. Methods: 23 questions survey focused on knowledge of endometriosis diagnosis distributed globally via patient- and community-endometriosis groups using social media. Main outcomes and measures: Descriptive data of the knowledge of diagnostic tools for diagnosing endometriosis, including details about diagnosis using ultrasound. Results: 84.0% of respondents had been previously diagnosed with endometriosis, 71.5% of which were diagnosed at the time of surgery. Ultrasound and MRI were the methods of diagnosis in 6.5% and 1.8%, respectively. 91.8%, 28.8%, and 16.6% of respondents believed surgery, ultrasound and MRI could diagnose endometriosis, respectively (more than one answer allowed). In those diagnosed by surgery, 21.7% knew about ultrasound as a diagnosis method compared to 51.5% knowing in those diagnosed non-surgically (p<0.001). 14.7%, 31.1%, and 18.2% stated superficial, ovarian, and deep endometriosis could be diagnosed with ultrasound (32.9% stated they did not know which phenotypes of endometriosis could be diagnosed). 58.4% of respondents do not believe they could access an advanced ultrasound in their region. Conclusions: There are significant gaps in the understanding of diagnosing endometriosis using non-surgical tools in this study population.

A document by Lara Lemon. Click on the document to view its contents.

Objective The My Baby’s Movements (MBM) trial aimed to evaluate the impact on stillbirth rates of a multifaceted awareness package (MBM intervention). Design Stepped-wedge cluster-randomised controlled trial. Setting Twenty-seven maternity hospitals in Australia and New Zealand. Population Women with a singleton pregnancy without major fetal anomaly ≥28 weeks’ gestation from August 2016-May 2019. Methods The MBM intervention was implemented at randomly assigned time points with sequential introduction into 8 clusters of 3-5 hospitals at four-monthly intervals. The stillbirth rate was compared in the control and intervention periods. Generalised linear mixed models controlled for calendar time, clustering, and hospital effects. Outcome Measures Stillbirth at ≥28 weeks’ gestation. Results There were 304,853 births with 290,219 meeting inclusion criteria: 150,079 in control and 140,140 in intervention periods. The stillbirth rate during the intervention was lower than the control period (2.2/1000 births versus 2.4, odds ratio [OR] 0.91, 95% Confidence Intervals [CI] 0.78-1.06, p=0.22). The decrease was larger across calendar time with 2.7/1000 in the first 18 months versus 2.0/1000 in the last 18 months (OR 0.74; 95% CI 0.63-0.86; p≤0.01). Following adjustment, stillbirth rates between the control and intervention periods were not significantly different: (aOR 1.18, 95% CI 0.93-1.50; p=0.18). No increase in secondary outcomes, including obstetric intervention or adverse neonatal outcome, was evident. Conclusion The MBM intervention did not reduce stillbirths beyond the downward trend over time, suggesting hospitals may have implemented best practice in DFM management outside their randomisation schedule. The role of interventions for raising awareness of DFM remains unclear

A document by Joan Lalor. Click on the document to view its contents.

Objective To assess if delivery mode and duration of labour in a first labour of spontaneous onset is associated with gestational length, delivery mode 3and neonatal outcome in the subsequent pregnancy. Study Design Retrospective analysis of prospectively collected data. Setting 15 Maternity units in North West London (1988 to 2000). Population 30,840 women with spontaneous onset of labour in pregnancy 1 and a subsequent birth reported in the same database. Methods Assessment of outcomes by mode of delivery in pregnancy 1, restricting the analysis to the difference in the gestational length between pregnancy 1 and 2. Main Outcome Measures Gestational length, mode of delivery and neonatal unit admission in pregnancy 2. Results Caesarean section (CS) in the first or second stage of labour in pregnancy 1 was associated with pregnancy 2 being a median of 5 and 8 days shorter and a preterm birth rate of 6.0% and 10.1% respectively, whereas following a spontaneous or instrumental birth in pregnancy 1 the median duration was similar, with preterm delivery rates of 4.5% and 3.9%. 56.2% of women with a CS in pregnancy 1 had a repeat CS and 12.5% of their babies were admitted to neonatal unit, compared with 5.3% of women with vaginal birth. Longer labours were associated with shorter gestations in pregnancy 2. Conclusions Compared to vaginal birth, an emergency CS in the first term pregnancy is associated with a shorter gestational length, increased rate of repeat CS and increased risk of NNU admission in the next pregnancy.

Objective To test the hypothesis that there is seasonal variation in the rates of gestational diabetes (GDM) diagnosed using a 2 hour oral glucose tolerance test. Design Monthly assessment of the percentage of women screened from 1st April 2016 to the 31st December 2020 who were diagnosed as having gestational diabetes Setting London Teaching Hospital Population 28,128 women receiving antenatal care between April 1st 2016 and 31 December 2020. Methods Retrospective study of prospectively collected data. Main Outcome Measures Proportion of women screened diagnosed as having gestational diabetes. Results The mean (SD) percentage of women diagnosed with GDM was 14.78 (2.24) in summer (June, July, August) compared with 11.23 (1.62) in winter (p < 0.001), 12.13 (1.94) in spring (p = 0.002), and 11.88 (2.67) in autumn (p = 0.003). There was a highly significant positive correlation of the percentage testing positive for GDM with the mean maximum monthly temperature (R2 = 0.248, p < 0.001). There was a statistically significant 33.8% increase in the proportion of GDM diagnoses from June 2020 onwards, possibly related to a reduction in exercise secondary to the Covid-19 pandemic. Conclusions There is a 23.3% higher rate of GDM diagnoses in the warmer summer months. There has been a 33.8% rise in GDM diagnoses associated with the Covid-19 pandemic.

BJOG exchange

Background Pregnancy and liver cirrhosis is a rare but increasing combination. Liver cirrhosis can raise the chance of maternal and fetal mortality and morbidity, although the exact risks remain unclear. Objective To provide a systematic literature review and meta-analysis on maternal, fetal and obstetric complications among pregnant women with liver cirrhosis. Search strategy We performed a systematic literature search in the databases PubMed/MEDLINE and EMBASE (Ovid) from inception through 25 January 2021. Selection criteria Studies including pregnancies with liver cirrhosis and controls were eligible. Data collection and analysis Two reviewers independently evaluated study eligibility. We used the random-effects model for meta-analysis. Main results Our search yielded 3118 unique papers. We included 11 studies, including 2912 pregnancies in women with cirrhosis from 1982-2020. Seven studies were eligible for inclusion in the meta-analysis. The overall maternal mortality rate was 0.89%. Maternal mortality and variceal hemorrhage decreased comparing recent and older studies. Most cases of maternal mortality due to variceal hemorrhage (70%) occurred during vaginal delivery. Pregnant women with liver cirrhosis had a higher chance of preterm delivery (OR 6.7 95% CI 5.1- 9.1), cesarean section (OR 2.6, 95% CI 1.7-3.9), preeclampsia (OR 3.8, 95% CI 2.2-6.5) and small for gestational age neonates (OR 2.6, 95% CI 1.6-4.2) compared to the general obstetric population. Subgroup-analyses could not be conducted. Conclusions Liver cirrhosis in pregnant women is associated with serious increases in maternal mortality and obstetric and fetal complications. Large international prospective studies are needed to identify risk factors for unfavorable outcome.