Sir,We welcome Gurol‐Urganci I and Bidwell et al’s evaluation of the impact of the care bundle to reduce obstetric anal sphincter injury (OASI) published in your August edition last year. The article reports much needed evidence on the efficacy of an intervention that has already taken hold in many maternity services across the country.Despite the article’s timely nature, we would like to voice our disappointment in the quality of the evidence of support for the care bundle Meulen and Thakar et al provide, and the recommendations made. The article fails to consider important evidence in this area of maternity care prompting this response. In particular, the authors miss the opportunity to contextualise the relatively low-level evidence they take from five articles – reporting three Scandinavian cohort studies and one educational intervention study on manual assistance during the final part of the second stage of labour (including gripping the baby’s chin through the perineum) - with the compelling findings from the Cochrane review on Perineal techniques during the second stage of labour for reducing perineal trauma.  This omission is important because the Cochrane review indicates that warm compresses have a bigger positive effect on OASI than the OASI care bundle reported by Meulen and Thakar et al’s. Furthermore, the Cochrane review provides evidence suggesting that hands off the perineum may protect women from episiotomy; an outcome which Meulen and Thakar et al acknowledge remained unchanged despite the third component in the care bundle aiming to ‘use of episiotomy when clinically indicated’. The selective nature of the evidence quoted, undermines the credibility of inferences that can be made from the findings. We suggest therefore, that caution should be taken when reading the authors conclusions.Our second concern rests upon the authors failure to account for the surprisingly small positive effect of the care bundle compared with the Scandinavian studies they quote. Meulen and Thakar et al report a 0.3% decrease in OASI compared with a 3.6% reduction;3% reduction; a 2.6% reduction for low risk women; and a 2.1% reduction in the various observational studies  Such a small effect in an open trial could easily be caused by ascertainment bias. Again, the quality of the previous Scandinavian studies make interpretation difficult but the marked difference in results between Scandinavia and England suggests caution should be taken when reading the authors conclusions.Our final concern pertains to women’s experience of the care bundle. Not only is the acceptability of the intervention not considered in this evaluation – a significant oversight given the conspicuous lack of evidence on this – there are ethical issues within the evaluation that deserve attention. The intervention description in figure 1 claims that women were informed about what could be done to reduce OASI. This does not appear to be entirely true given the lack of consideration of warm compresses and hands off to protect against episiotomy. Even more unsettling is the statement ‘MPP should be used unless the woman objects’, implying little consideration for autonomy and informed consent.For the above reasons, we are not only disappointed with the BJOG article but with the professional stakeholder investment in the intervention which seems to have been widely and uncritically supported, with some support even being somewhat evangelical, despite the limited evidence for support.Signatures,
Letter to editor: “Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial “Cheng-Yang Hsu1, Ching-Hu Wu1, Cheng-Yu Long1, 21 Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan2 Department of Obstetrics and Gynecology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanRunning head: Two prospective for this promising experimentWords Count: 315Corresponding Author:Dr. Cheng-Yu Long, MD, PhD, Department of Obstetrics and Gynaecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100, Shih-Chuan 1st Rd, Kaohsiung 80708, TaiwanE-mail: firstname.lastname@example.orgDear Editor-in Chief:We read with great interest with recent publication in BJOG by Mackova et al. (1) This study describe effects of non-ablative erbium-doped: yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. The ewes were randomized to three groups: vaginal Er:YAG laser application, estrogen replacement, and sham groups.In the estrogen replacement group of ewes, an estrogen implant was inserted under the skin in the inguinal region. The result showed increase in epithelia thickness in vaginal biopsies and it was significantly higher compared with the laser application and sham groups. In all groups, the lamina propria did not showed any significant differences. Also the autopsy showed the uterus of estrogen-exposed ewes weighted more.We would like to humbly comment the vaginal estrogen use and laser application in genitourinary syndrome of menopause.The vaginal estrogen application was given twice a week with the cream in currently practice of female who suffered from genitourinary syndrome of menopause (GSM). Firstly, the vaginal estrogen application was given twice a week with the cream in clinical practice of female who suffered from GSM. The administration showed improvement of the symptoms while no significant change in serum estrogen level. (2) The estrogen implant in the ewe experiment continues to release estrogen and caused sustained estrogen effect in the ewe and caused gaining weight of uterus, which was very different with our clinical practice of intermittent vaginal cream use.Second, the application in this study is Er:YAG laser, with the the lesser wave length: 2940 nm. While the CO2 laser had much longer wave length 10600 nm and had deeper effect in not only vaginal epithelium but also lamina propia. (3) Therefore the vascularization effects of lamina propia may be obvious noticeably.We thought these 2 flaws could be revised to make the ewe experiment more accurate and similar to current management in women with GSM.ReferencesMackova KA-OX, Mazzer AM, Mori Da Cunha MA-O, Hajkova Hympanova LA-O, Urbankova IA-O, Kastelein AA-O, et al. Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial. BJOG . 2021 May;128(6):1087-1096.Long CY, Liu CM, Hsu SC, Wu CH, Wang CL, Tsai EM. A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women. Menopause . Sep-Oct 2006;13(5):737-43.Bhide AA, Khullar V, Swift S, Digesu GA. The use of laser in urogynaecology. Int Urogynecol J . 2019 May;30(5):683-692.
BJOG-20-1830.R3: The levonorgestrel intrauterine system versus endometrial ablation: when the choice of treatment goes beyond its efficacy Author: Sarah Maheux-LacroixEndometrial ablation and levonorgestrel intra-uterine system (LNG-IUS) are two well-established treatment options for women with heavy menstrual bleeding (Bergeron C, Hum Reprod Update 2020;26(2):302-11) that have contributed to the important decrease in hysterectomies over the last decades (Bergeron AM et al. J Obstet Gynaecol Can 2020;42(12):1469-74). Van den Brick et al. present a cost-effectiveness analysis comparing the two options, in which a treatment strategy starting with the LNG-IUS is less costly than a strategy starting with endometrial ablation. Up to now, economic analyzes mostly relied on simulation modeling and conclusions could vary depending on assumptions for efficacy and discontinuation in each arm. This study was based on actual data from an RCT with a 2-year follow-up.Despite the 43% discontinuation rate for LNG-IUS, this method was cheaper at 2 years and this conclusion stood up to sensitivity analyzes. The LNG-IUS remained superior despite the assumption of an ambulatory setting for endometrial ablation, but this analysis needs to be interpreted with caution. Data was lacking on costs of the outpatient setting and saving of only \euro111 was estimated when comparing to the inpatient setting (\euro2,241 versus \euro2,352). In other studies, the outpatient hysteroscopy was associated with substantial savings, being 2 to 4 times cheaper (Bennett A et al. J Obstet Gynaecol Can 2019;41(7) :930-41). Indeed, costs are always subject to vary from region to region with possibly different conclusions in different settings, but clearly an outpatient procedure reduces the cost difference between the two methods.Beyond 2 years, data is lacking. The two methods have been compared in RCT at up to 5 years (Bergeron C, Hum Reprod Update 2020;26(2):302-11) and we do not know if one method is superior the other to prevent longer term failures and re-interventions. The LNG-IUS requires replacement every 5 years but seems to decrease the risk of eventually requiring a hysterectomy in younger patient (Bergeron C, Hum Reprod Update 2020;26(2):302-11). Both factors could have an impact in a longer-term cost-effectiveness analysis and underline that future research should investigate the modifying effect of age.At the end of the day, the choice of treatment needs to be individualized to the patient needs and preferences. Certain characteristics lead us to favor the LNG-IUS, such as need for contraception, wish to preserve fertility, risk of endometrial neoplasia or presence of concomitant gynecologic conditions such as adenomyosis. On the other hand, some women do not tolerate or refuse potential side effects of hormones. Let’s keep in mind that both methods are effective, minimally invasive and represent substantial savings compared to a hysterectomy, but when both options are adequate for a patient, the LNG-IUS is less costly for society.
Medical Management of GDM – following the evidenceMini Commentary on 21-0353.R1 - “Changing Patterns in Medication Prescription for Gestational Diabetes During a Time of Guideline Change in the USA: A Cross-sectional Study ”Aaron B. Caughey, MD, PhDDepartment of Obstetrics and Gynecology; Oregon Health & Science University; Portland, ORCorrespondence:Aaron B. Caughey, MD, PhDProfessor and ChairDepartment of Obstetrics and GynecologyOregon Health & Sciences UniversityP: 503-494-2999F: 503-494-2391E: email@example.comGestational diabetes mellitus (GDM) is one of the most common pregnancy complications and is associated with numerous pregnancy complications including preeclampsia, preterm birth, stillbirth, cesarean delivery, fetal macrosomia, birth injury, neonatal hypoglycemia, childhood obesity in the offspring and other short- and long-term complications.(Sweeting AN, et al. Diabetes Care. 2016;39:75-81) Many of these complications appear to be associated with hyperglycemia, so tight control of maternal plasma glucose is the primary approach to management during pregnancy. The first line approach is usually a strict carbohydrate-controlled diet and exercise, but when this fails, medical therapy is indicated.For many years, the first-line medical approach was injectable insulin. However, an oral hypoglycemic agent, glyburide, was increasingly adopted after a trial of glyburide versus insulin demonstrated no statistical difference in the outcomes, though it was underpowered to do so.(Langer O, et al. N Engl J Med 2000;343:1134-8) Another oral agent, metformin, was studied in an adequately powered randomized trial that found no differences in outcomes between pregnancies treated with metformin versus insulin.(Rowan JA, et al. N Engl J Med 2008;358:2003-15) Perhaps because glyburide was already being used, or that metformin crosses the placenta, or an odd finding of a higher rate of preterm birth in the metformin group, there was little adoption of metformin after this trial. Other trials of these medications have been conducted and a systematic review in 2015 demonstrated that a number of outcomes were worse in women randomized to glyburide whereas there are no differences in women randomized to metformin.(Balsells M, et al. BMJ 2015;350:h102) These findings led the American College of Obstetricians and Gynecologists (ACOG) to change their recommendations to encourage insulin to be first-line treatment in 2017.(ACOG. Obstet Gynecol. 2017;130:e17-e37) A follow-up recommendation from ACOG broadened to include metformin as well.(ACOG. Obstet Gynecol. 2018 Feb;131(2):e49-e64)So, how have these data and the recommendations from ACOG changed practice patterns? In a paper published in BJOG this month, the authors examined the pharmacologic approaches to management in GDM.(Venkatesh KK, et al. BJOG, 2021) In a large cohort of over 10,000 individuals with GDM requiring medical therapy, they found that from 2015 to 2018, the use of insulin increased from 26% to 44%, the use of metformin increased from 17% to 29%, and the use of glyburide decreased from 58% to 27%. These data are from either side of the 2017 ACOG recommendation, but end in the same year as the follow-up recommendation. Given how long it can take for recommendations to be adopted by clinicians, one wonders how the practice patterns may have continued to evolve in 2019 and 2020.Recalling that the 2017 ACOG recommendation was to have insulin be first line for GDM, while the trend is in the right direction, it was still less than 50% as of 2018. While it is understandable that clinicians and patients want to prescribe an oral agent, insulin remains an effective medication with great safety data. Likely this is why it is recommended as first-line treatment by many organizations and hopefully, further trends towards its primary use will be seen.
Mini-Commentary on Manuscript # BJOG-20-2493A Biomarker for Amniotic Fluid Embolism: The Search ContinuesWord count: 495Research into the pregnancy associated cytokine storm-like condition historically known as amniotic fluid embolism (AFE) has been hampered by a lack of unique diagnostic criteria. In its classic form, the clinical presentation of this condition is unmistakable. In less classic presentations, each of the clinical hallmarks of AFE (depressed ventricular function, lung injury and coagulopathy) may, in isolation, be seen in other obstetric conditions. Indeed, much of the confusion arising from previously published case series purporting to describe women with AFE appears to be the result of the inclusion of patients with other conditions. (Clark SL et al Obstet Gynecol 2014:123: 337-48) Identification of a reliable, objective biomarker specific to AFE is badly needed.It is against this background that the work of Bouvet et al is especially welcome. These investigators examined the use of insulin-like growth factor binding protein -1, a protein found in high concentration in amniotic fluid, as a potential biomarker of AFE in women suspected to have this condition. Unfortunately, the results were negative, leading the authors to question the usefulness of this assay.Although the results were negative, the major importance of this study may be as an example of how to properly conduct a search for AFE biomarkers. These authors avoided several pitfalls that have invalidated most previous biomarker publications. First, they used 2 objective, internationally recognized clinical criteria sets for identifying women with AFE. Their finding that only about half of women suspected to have AFE actually had the condition based on either of the identified criteria sets emphasizes the importance of insisting on inclusion criteria more stringent than “someone thought the patient had AFE,” so common in current literature. Secondly, in their use of women with suspected AFE these investigators avoided another common pitfall in biomarker research, namely the use of normal pregnant women, rather than critically ill women as controls. Presumably the women without AFE had some other form of critical illness. This distinction is particularly important in investigating the potential of various inflammatory mediators as specific markers for AFE.Finally, the authors’ data support 2 additional important conclusions beyond the original intent of the paper. The finding that 100% of AFE patients identified by the SMFM criteria also met the UK diagnostic criteria serve as additional validation of the ability of the former criteria to reliably identify a group of women who, for research purposes, do have the disease, while excluding some others with less typical forms of AFE. (Clark et al, Am J Obstet Gynecol 2016:408-12.) Secondly, the authors’ findings of no difference in levels of ILGFBP-1 in women with and without clinical AFE, despite high levels of this protein in amniotic fluid, supports the current belief that amniotic fluid per se is unrelated to the condition known as amniotic fluid embolism.It is generally accepted by the scientific community that AFE is unpreventable. It is hoped that additional quality research such as that of Bouvet et al may someday change this unfortunate fact.
Professor PEP Petros DSc DS (UWA) PhD (Uppsala) MB BS MD (Syd) FRCOG (Lond)31/93 Elizabeth Bay Rd, Elizabeth Bay NSW 2011 AUSTRALIAReconstructive Pelvic Floor Surgeon and Certified Urogynaecologist (retired)Formerly University of NSW Professorial Dept of Surgery, St Vincent’s Hospital Sydney (retired)Adjunct Professor, University of Western Australia School of Mechanical and Chemical Engineering, Perth WA (current)Tel 61 2 9361 3853 Cellphone (AUST) 61 411 181 731Email firstname.lastname@example.org website www.integraltheory.org
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.
Aortic balloon for the intraoperative management of placenta accreta spectrum: need for standardised methodology and safety dataIn 2003, Bell-Thomas et al (BJOG 2003;110:1120-1122) reported on the emergency use of a transfemoral aortic occlusion catheter to control massive haemorrhage in a case of caesarean hysterectomy for placenta percreta. This was only the second case published in the international literature on the use of an intra-abdominal aortic balloon occlusion (IABO) in the management of placenta accreta spectrum (PAS) (Paull et al. Anesth Intensive Care 1995;23:731-734). A non-exhaustive Pub-Med literature review of articles published in English on this the topic over the last 20 years, identifies 27 articles, 23 of which come from the Peoples Republic of China, where IABO seems to be increasingly popular in the management of PAS.In brief, IABO involves the insertion of a balloon catheter into the infrarenal abdominal aorta above the aortic bifurcation under fluoroscopy guidance. The procedure is performed in a hybrid operating room or interventional radiology (IR) suite with secondary transfer to the operating room. In all but one study (Zhu et al Biomed Res Int.2017:8604849), the balloon was inflated after delivery of the newborn.All publications so far have been retrospective and most are case-control studies, comparing the outcomes of IABO with those of routine surgical techniques with or without additional procedures such as intra-uterine tamponade. Recently, authors have also started to compare IABO with iliac artery balloon occlusion.Overall, these studies have shown that IABO is associated with reduced estimated blood loss and transfusion requirement, ICU admission and hysterectomy and suggested that IABO is more effective than iliac artery balloon occlusion, presumably as arterial occlusion is more effective.However, there is wide variation between studies in prenatal imaging and clinical selection criteria, intraoperative IR methodology and confirmation of the diagnosis of PAS at birth. For example, the pre-operative fluoroscopy time ranges between 2 and 25 minutes with fetal radiation exposure of 4 to 25 mGy; intraoperative balloon inflation/deflation time varies between 5-10/1 minutes and 45-80/10 minutes. The size of the balloon and the need for transfer between the IR room and the operative theatre is rarely described. Most studies lack histopathology confirmation of the diagnosis and/or stratification by PAS grade.Heterogeneity in methodology and design leads to a high risk of confounding, bias or chance. There is also a high risk that the relationship is not causal. One major concern is the risks-benefit ratio of the use of IABO for both mothers and fetuses, in particular if they do not have PAS. The most commonly reported post-operative complication associated with IABO are arterial thrombosis of the external iliac or the femoral artery. There are no data on the long-term follow of the children born after IABO.In 2018, the expert panel of the RCOG green top guidelines 27a (Jauniaux et al., BJOG.2019;126:e1-e48) concluded that larger studies are necessary to determine the safety and efficacy of IR before this technique can be advised in the routine management of PAS. The 10 new studies published in 2019-2010 on the use of IABO in the management of PAS are insufficient to change this statement.Word count: 499
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.
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’.