Mini Commentary – BJOG

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

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:[email protected]: 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.

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

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.

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.

A document by Alexandra Emms. Click on the document to view its contents.

Letter to the Editor, BJOG Title: ESMiE confidential enquiry: Broader view besides focus on errors by birth-attendants.Re: Rowe R, Draper ES, Kenyon S, Bevan C, Dickens J, Forrester M, Scanlan R, Tuffnell D, Kurinczuk JJ. Intrapartum-related perinatal deaths in births planned in midwifery-led settings in Great Britain: findings and recommendations from the ESMiE confidential enquiry. BJOG 2020;127:1665–1675.Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKShort running title: ESMiE enquiry: broader viewEmail: [email protected] Tel: 07906620662Word 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.

Objective: To determine the incidence of and risk factors for perioperative blood transfusions after urogenital fistula repairs in Uganda. Design: A retrospective cohort study. Setting: A community hospital in Masaka, Uganda. Population: Women who underwent fistula repair at the Kitovu Hospital between 2013 and 2019. Methods: Retrospective review of demographics, and clinical perioperative characteristics of patients surgically treated for urogenital fistula. Patient characteristics were compared between those who did and did not require a blood transfusion. Main Outcome Measures: need for perioperative blood transfusion, risk factors Results: 546 patients treated for urogenital fistulas were included in this study. The median age was 31.1 ± 13.2. A vaginal surgical approach was used in the majority of patients (84.6%). Complications occurred in 3.5% of surgical repairs, and the incidence of blood transfusions was 6.2%. In multivariable analyses, women with fistula repairs approached abdominally were 4.3 (95% CI: 1.85–10.00) times more likely to require transfusions than vaginal operations. A borderline association was observed between timing of repair and perioperative transfusions such that patients who underwent repair after three months from the time of developing the fistula were at lower risk of perioperative transfusions (aOR: 0.48, 95% CI: 0.22–1.04). Conclusions: The incidence of blood transfusions among urogenital fistula repairs in our population is twice that of developed nations. An abdominal surgical approach to urogenital fistula is a significant risk factor for perioperative blood transfusions. Timing of repair may warrant further study.

Background Pregnancy and childbirth increase the risk for pelvic floor dysfunction, including sexual dysfunction. So far, the mechanisms and the extent to which certain risk factors play a role, remain unclear. Objectives In this systematic review of literature, we aimed to determine the risk factors for sexual dysfunction in the first year after delivery. Search Strategy We searched MEDLINE, Embase and CENTRAL using the search strategy: Sexual dysfunction AND Obstetric events. Selection Criteria We included original English, comparative studies that used validated questionnaires and the ICS/IUGA terminology for sexual dysfunction, dyspareunia and vaginal dryness. Data Collection and Analysis We assessed the quality and the risk of bias of the included studies with the Newcastle Ottawa Scale. We extracted the reported data and we performed random-effects meta-analysis to obtain the summary Odds Ratios (OR) with 95% Confidence Intervals. Heterogeneity across studies was assessed using the I2 statistic. Main Results We found no significant difference in the odds for both sexual dysfunction and dyspareunia between cesarean section and spontaneous delivery (OR:1.17[0.88-1.57] and OR:0.75[0.53-1.07]) and between operative delivery and spontaneous delivery (OR:1.56[0.87-2.79] and OR:1.35[0.75-2.42]). Anal sphincter injury was associated with increased odds for both sexual dysfunction (OR:3.00[1.28-7.03]) and dyspareunia (OR:1.71[1.09-2.67]). Episiotomy was associated with dyspareunia (OR:1.65[1.20-2.29]) but not with sexual dysfunction (OR:1.90[0.94-3.84]). We retrieved one study of low quality which reported on vaginal dryness and found no significant association with obstetric events.

Objective To develop a Core Outcome Set (COS) for treatment of perinatal depression Design Systematic overview of outcomes reported in the literature and consensus development study using a Delphi survey and modified nominal group technique. Setting International. Population Two hundred and twenty-two participants, representing thirteen countries. Methods A systematic overview of outcomes reported in recently published research, a two-round Delphi survey, a consensus meeting at which the final COS was decided. Main results In the literature search, 1772 abstracts were identified and evaluated, 284 papers/protocols were assessed in full and 165 studies were finally included in the review. In all, 106 outcomes were identified and thus included in the Delphi survey. 222 participants registered for the first round of the Delphi survey and 151 (68%) responded. In the second round, 123 (55%) participants responded. The following 9 outcomes were agreed upon for inclusion in the final COS: self-assessed symptoms of depression, diagnosis of depression by a clinician, parent to infant bonding, self-assessed symptoms of anxiety, quality of life, satisfaction with intervention, suicidal thoughts, attempted or committed suicide, thoughts of harming the baby, and adverse events. Conclusions The relevant stakeholders prioritised outcomes and reached consensus on a COS comprising nine outcomes. We hope that this COS will contribute to consistency and uniformity of outcome selection and reporting in future clinical trials involving treatment of perinatal depression Funding This article is adapted from a report by SBU, which provided funding for the study. Keywords: perinatal depression, postpartum depression, antenatal depression, COS

Objectives: to evaluate the effectiveness of uterine tamponade devices for atonic refractory postpartum haemorrhage (PPH) after vaginal birth, and the effect of including uterine tamponade devices in institutional protocols. Search strategy: databases in PubMed, EMBASE, CINAHL, LILACS and POPLINE. Study selection: randomised and non-randomised comparative studies. Outcomes: composite outcome including surgical interventions (artery ligations, uterine compressive sutures or hysterectomy) or maternal death, and hysterectomy. Results: all four included studies were at high risk of bias. The certainty of evidence rated as very low to low. One randomised study measured the effect of the the condom-catheter balloon compared to standard care and found unclear results for the composite outcome (RR 2.33, 95%CI 0.76-7.14) and hysterectomy (RR 4.14, 95%CI 0.48-35.93). Three comparative studies assessed the effect of including UBTs in institutional protocols. A stepped-wedge study suggested an increase in the composite outcome (RR 4.08, 95%CI 1.07-15.58), and unclear results for hysterectomy (RR 4.38, 95% CI 0.47-41.09) with the use of the condom-catheter or surgical glove balloon. One non-randomised study showed unclear effects on the composite outcome (RR 0.33, 95%CI 0.11-1.03) and hysterectomy (RR 0.49, 95%CI 0.04-5.38) after the inclusion of Bakri balloon. The second non-randomized study found unclear effects on the composite outcome (RR 0.95, 95%CI 0.32-2.81) and hysterectomy (RR 1.84, 95%CI 0.44-7.69) after the inclusion of Ebb or Bakri balloon. Conclusions: the effect of uterine tamponade devices for the management of atonic refractory PPH after vaginal delivery is unclear, as is the role of the type of device and the setting.

Objective Post-menopausal nocturia is poorly understood. This study aimed to identify hormonal and lifestyle factors associated with nocturia and to understand the relative contribution of altered urine production and bladder storage dysfunction in women. Design, setting, population and methods Women ≥40 years presenting to public continence services were enrolled in a cross-sectional study. 153 participants completed a hormone status questionnaire, a validated nocturia causality screening tool and a 3-day bladder diary. Descriptive statistics and logistic regression models for nocturia severity and bladder diary parameters were computed. Results Overall, 91.5 % reported nocturia, 55% ≥2 /night. There was a difference of 167.5 mL (p<0.001) in nocturnal urine volume between women with nocturia ≥2 (median 736mL) vs less often (517mL). Significant predictors of self-reported disruptive nocturia were age (OR 1.04, 95%CI 1.002-1.073) and vitamin D supplementation (OR 2.33, 95%CI 1.11-4.91). Nocturnal polyuria was significantly more common with nocturia ≥2 compared to less often (p<0.002). 150 minutes of exercise per week was protective for nocturnal polyuria (OR 0.22, p=0.001). Nocturia index >1.3 was significantly predicted by age (OR 1.07, p<0.001), regular exercise (OR 0.41, p=0.036), day flushes (OR 4.00, p=0.013) and use of Vitamin D (OR 2.34, p=0.043). Maximum voided volumes were significantly lower with nocturia≥2 vs less often (night: 268ml vs 350mL; day: 200mL vs 290mL). Conclusions Bothersome nocturia in post-menopausal women is associated with changes to both nocturnal diuresis and bladder storage. Regular physical activity, prolapse reduction and oestrogen replacement may be adjunctive in managing bothersome nocturia in women.