Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial. (2020)

Type of publication:
Randomised controlled trial

Author(s):
Chu, Justin J; Devall, Adam J; Beeson, Leanne E; Hardy, Pollyanna; Cheed, Versha; Sun, Yongzhong; Roberts, Tracy E; Ogwulu, C Okeke; Williams, Eleanor; Jones, Laura L; La Fontaine Papadopoulos, Jenny H; Bender-Atik, Ruth; Brewin, Jane; Hinshaw, Kim; Choudhary, Meenakshi; Ahmed, Amna; Naftalin, Joel; Nunes, Natalie; Oliver, Abigail; Izzat, Feras; Bhatia, Kalsang; Hassan, Ismail; Jeve, Yadava; Hamilton, Judith; Deb, Shilpa; Bottomley, Cecilia; Ross, Jackie; Watkins, Linda; *Underwood, Martyn; Cheong, Ying; Kumar, Chitra S; Gupta, Pratima; Small, Rachel; Pringle, Stewart; Hodge, Frances; Shahid, Anupama; Gallos, Ioannis D; Horne, Andrew W; Quenby, Siobhan; Coomarasamy, Arri

Citation:
Lancet; Aug 2020 [epub ahead of print]

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

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The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM Trial (2020)

Type of publication:
Journal article

Author(s):
CB Okeke Ogwulu, I Goranitis, AJ Devall, V Cheed, ID Gallos, LJ Middleton, HM Harb, HM Williams, A Eapen, JP Daniels, A Ahmed, R Bender‐Atik, K Bhatia, C Bottomley, J Brewin, M Choudhary, S Deb, WC Duncan, AK Ewer, K Hinshaw, T Holland, F Izzat, J Johns, M Lumsden, P Manda, JE Norman, N Nunes, CE Overton, K Kriedt, S Quenby, S Rao, J Ross, A Shahid, *M Underwood , N Vaithilingham, L Watkins, C Wykes, AW Horne, D Jurkovic, A Coomarasamy, TE Roberts

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology; May 2020; Vol 127 (no. 6); p. 757-767

Abstract:
Objectives: To assess the cost‐effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding.
Design: Economic evaluation alongside a large multi‐centre randomised placebo‐controlled trial.
Setting: Forty‐eight UK NHS early pregnancy units.
Population: Four thousand one hundred and fifty‐three women aged 16–39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac.
Methods: An incremental cost‐effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages.
Main outcome measures: Cost per additional live birth at ≥34 weeks of gestation.
Results: Progesterone intervention led to an effect difference of 0.022 (95% CI −0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI −£559 to £711) more than the mean cost in the placebo group. The incremental cost‐effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014–0.096) and this was associated with a cost saving of £322 (95% CI −£1318 to £673).
Conclusions: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost‐effective intervention, particularly for women with previous miscarriage(s).

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The incidence of and risk factors for a repeat obstetric anal sphincter injury (OASIS) in the vaginal birth subsequent to a first episode of OASIS: a hospital-based cohort study (2017)

Type of publication:
Journal article

Author(s):
*Antonakou, Angeliki; *Papoutsis, Dimitrios; *Henderson, Karen; *Qadri, Zahid; *Tapp, Andrew

Citation:
Archives of gynecology and obstetrics. Vol 295(5):1201-1209

Abstract:
PURPOSETo identify the incidence of and risk factors for a repeat obstetric anal sphincter injury (OASIS) in women who sustained an OASIS in their first vaginal delivery and have a subsequent vaginal birth.METHODS Data were collected retrospectively for women having had singleton cephalic presentation vaginal deliveries between 2007 and 2015. Women with breech deliveries, stillbirths, foetal congenital abnormalities and multiple pregnancies were excluded.RESULTSOver the study period, we identified 11,191 women who had a first vaginal birth, of which 603 (5.4%) sustained a first episode of OASIS. Of these women, 243 (40.2%) had a subsequent pregnancy with 190 (78.1%) having a second vaginal birth, 13 (5.4%) an emergency caesarean section (CS) delivery while in labour and 40 (16.5%) an elective CS delivery. In those who delivered vaginally, 16 (8.4%) women had a repeat OASIS. After adjusting for several confounding factors, it was found that the risk of a repeat OASIS was associated with the use of epidural analgesia (OR = 3.66; 95% CI:1.14-11.71) and an episiotomy in the first delivery (OR = 3.93; 95% CI:1. 03-15.02) and a short labour (<2.8 h) in the second delivery (OR = 14.55; 95% CI: 1.83-115.75). The time interval between the two vaginal births was not associated with any increased risk of a repeat OASIS.CONCLUSION We found that 8.4% of women sustained a repeat OASIS in a subsequent vaginal birth with this risk being associated with the presence of a short second labour and certain features from the first labour.

Perineal support and risk of obstetric anal sphincter injuries: a Delphi survey (2015)

Type of publication:
Journal article

Author(s):
Ismail KM, Paschetta E, *Papoutsis D, Freeman RM

Citation:
Acta Obstetricia Et Gynecologica Scandinavica 2015 Feb; Vol. 94 (2), pp. 165-74. Date of Electronic Publication: 2014 Dec 30.

Abstract:
Objective: To explore the views of a multidisciplinary group of experts and achieve consensus on the importance of perineal support in preventing obstetric anal sphincter injuries (OASIS).
Design: A three-generational Delphi survey.
Setting: A UK-wide survey of experts.
Population: A panel of 20 members consisting of obstetricians, midwives and urogynecologists recommended by UK professional bodies.
Methods: A 58-item web-based questionnaire was sent to all participants who were asked to anonymously rate the importance of each item on a six-point Likert scale. They were asked to rate their level of agreement on statements related to hands-on/hands-poised techniques, the association of hands-poised/hands-off approach with OASIS, the need to implement perineal support and the need to improve the evidence to support it. Systematic feedback of responses from previous rounds was provided to participants.
Main Outcome Measures: To achieve consensus on key areas related to perineal support.
Results: The response rate was 100% in all three iterations. There was consensus that current UK practice regarding perineal protection was not based on robust evidence. The respondents agreed that hands-poised/hands-off and OASIS are causally related and that hands-poised was misinterpreted by clinicians as hands-off. Although 90% of experts agreed that some form of randomized trial was required and that all would be prepared to take part, there was also consensus (75%) that in the meantime, hands-on should be the recommended technique.
Conclusions: Our results highlight the current lack of evidence to support policies of perineal support at time of birth and the need to address this controversial issue.

Postpartum posterior reversible encephalopathy syndrome (PRES) in a twin pregnancy complicated by preeclampsia-eclampsia: Case report (2014)

Type of publication:
Journal article

Author(s):
*Papoutsis D., *El-Attabi N., *Sizer A.

Citation:
Clinical and Experimental Obstetrics and Gynecology, 2014, vol./is. 41/3(351-353), 0390-6663 (2014)

Abstract:
This is the second case in literature of posterior reversible encephalopathy syndrome (PRES) in a twin pregnancy complicated by preeclampsia-eclampsia. A 27-year-old primigravida with dichorionic diamniotic twin pregnancy was admitted at 36 weeks of gestation for induction of labour due to preeclampsia. On the second day postpartum, the patient developed severe hypertension, visual symptoms, confusion, headache, and eclamptic fits. Head computed tomography (CT) showed hypodense basal ganglia lesions. The patient was treated in the intensive treatment unit with hydralazine and labetalol infusions and anticonvulsants. Five days later, there was complete clinical improvement and follow-up magnetic resonance imaging (MRI) was normal. The patient was discharged 11 days post-delivery. Diagnosis of PRES is based on the presence of clinical features of acute neurologic compromise, abnormal neuroimaging findings, and complete reversibility of findings after prompt treatment. Early recognition and proper treatment result in complete reversibility of this condition.

 

Top 15 research priorities for preterm birth with clinicians and service users’ involvement-outcomes from a james lind alliance priority setting partnership (2014)

Type of publication:
Conference abstract

Author(s):
Uhm S., Alderdice F., Chambers B., Gyte G., Gale C., Duley L., James C.P., David A.L., McNeill J., Turner M.A., Shennan A., *Deshpande S., Crowe S., Chivers Z., Brady I., Oliver S.

Citation:
Archives of Disease in Childhood: Fetal and Neonatal Edition, June 2014, vol./is. 99/(A158), 1359-2998 (June 2014)

Abstract:
Background Preterm birth is the single most important determinant of adverse infant outcomes in terms of survival, quality of life, psychosocial and emotional impact on the family, and health care costs. Research agenda in this area has been determined primarily by researchers, and the processes for priority setting in research have often lacked transparency. Objectives To identify 15 most important priorities for future research for practitioners and service users in the area of preterm birth. Methods A priority setting partnership was established by involving clinicians, adults who were born preterm, and parents and families with experience of preterm birth. Research uncertainties were gathered from surveys of service users and clinicians, and analyses of systematic reviews and clinical guidance, and then prioritised in a transparent process, using a methodology advocated by the James Lind Alliance. Results 593 uncertainties were submitted by 386 respondents and 52 were identified from literature reviews. After merging similar questions, a long list of 104 questions were distributed for voting. The 30 most popular items were then prioritised at a workshop. The top 15 research priorities included prevention of preterm birth, management of neonatal infection, necrotising enterocolitis, pain and lung damage, care package at discharge, feeding strategies, pre-eclampsia, emotional and practical support, attachment and bonding, premature rupture of membranes and best time for cord clamping. Conclusions These top research priorities in preterm birth provide guidance for researchers and funding bodies to ensure that future research addresses questions that are important to both clinicians and service users.

Link to more details or full-text: http://fn.bmj.com/content/99/Suppl_1/A158.1.abstract

 

Does traction on the cervix under anaesthesia tell us when to perform a concomitant hysterectomy? A 2-year follow-up of a prospective cohort study (2014)

Type of publication:
Journal article

Author(s):
Madhu C., *Foon R., Agur W., Smith P.

Citation:
International Urogynecology Journal and Pelvic Floor Dysfunction, September 2014, vol./is. 25/9(1213-1217), 0937-3462;1433-3023 (September 2014)

Abstract:
Introduction and hypothesis: Variations exist in urogynaecological practice to decide on hysterectomy in managing prolapse. This study evaluates the outcomes of uterine preservation during anterior colporrhaphy with apparent uterine descent with cervical traction under anaesthesia. We hypothesize that cervical traction should not be used to assess uterine prolapse. Methods: Thirty-five women opting for surgery for symptomatic anterior prolapse (> stage 2) with no uterine prolapse (point C at -3 or above) were recruited. ”Validated cervical traction” was applied under anaesthesia. Only an anterior repair was performed. Incontinence Modular Questionnaire Vaginal Symptoms (ICIQ-VS) questionnaires were used for follow-up. Wilcoxon test was used for statistical analysis. Results: Stage 2 uterine prolapse (POPQ) was demonstrated in all women with traction under anaesthesia. Follow-up was possible in 29 women, 5 did not respond and 1 needed a hysterectomy at 6 months (2.86 %, 95 % CI 0.07-14.91 %). The mean follow-up time was 23 months (range: 13-34 months). There was a significant reduction in the ICIQ-VS scores from 22.7 (pre-operative) to 7.97 at 23 months (p

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A rare obstetric emergency: acute uterine torsion in a 32-week pregnancy (2014)

Type of publication:
Journal article

Author(s):
*Moores KL, *Wood MG, *Foon RP

Citation:
BMJ Case Reports, 2014, vol./is. 2014/, 1757-790X (2014)

Abstract:
Uterine torsion is rare in pregnancy and the cause in most cases is unknown. It is associated with fetal compromise, with perinatal mortality reported to be around 12%. Our case describes an acute torsion, presenting in pregnancy with severe abdominal pain and vomiting with a viable 32-week gestation. Emergency caesarean section was performed and the 180degree uterine torsion was diagnosed intraoperatively. Posterior hysterotomy was required for delivery prior to detorsion of the uterus. This report describes that prompt recognition and intraoperative vigilance can achieve a successful maternal and fetal outcome in this rare and difficult obstetric scenario.

Link to more details or full-text: http://casereports.bmj.com/content/2014/bcr-2013-202974.abstract

Torrential epistaxis in the third trimester: a management conundrum. (2014)

Author(s):
Crunkhorn RE, *Mitchell-Innes A, Muzaffar J

Citation:
BMJ Case Reports, 2014, vol./is. 2014/, 1757-790X (2014)

Abstract:
Although epistaxis is common during pregnancy, large volume epistaxis is rare. Many standard epistaxis management options are limited in pregnancy due to absolute or relative contraindications. Ear, nose and throat surgeons need to be aware of what options can be used safely and effectively. We present a case of a 32-year-old woman, 32 weeks pregnant, who was admitted with heavy epistaxis refractive to conservative management. Several potential interventions including bismuth iodoform paraffin paste (BIPP) and Floseal were contraindicated or involved additional risk in pregnancy necessitating unorthodox management. This challenging case highlights suitable alternatives for managing large volume epistaxis during pregnancy, as well as discussing the differential diagnosis and relevant investigations. 2014 BMJ Publishing Group Ltd.

Link to full-text: http://casereports.bmj.com/content/2014/bcr-2014-203892.abstract