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BMC Pregnancy and Childbirth
Published in: BMC Pregnancy and Childbirth 1/2019

Open Access 01-12-2019 | Fertility | Study protocol

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development – the 2Close study: a multicentre randomised controlled trial

Authors: S. I. Stegwee, I. P. M. Jordans, L. F. van der Voet, M. Y. Bongers, C. J. M. de Groot, C. B. Lambalk, R. A. de Leeuw, W. J. K. Hehenkamp, P. M. van de Ven, J. E. Bosmans, E. Pajkrt, E. A. Bakkum, C. M. Radder, M. Hemelaar, W. M. van Baal, H. Visser, J. O. E. H. van Laar, H. A. A. M. van Vliet, R. J. P. Rijnders, M. Sueters, C. A. H. Janssen, W. Hermes, A. H. Feitsma, K. Kapiteijn, H. C. J. Scheepers, J. Langenveld, K. de Boer, S. F. P. J. Coppus, D. H. Schippers, A. L. M. Oei, M. Kaplan, D. N. M. Papatsonis, L. H. M. de Vleeschouwer, E. van Beek, M. N. Bekker, A. J. M. Huisjes, W. J. Meijer, K. L. Deurloo, E. M. A. Boormans, H. W. F. van Eijndhoven, J. A. F. Huirne

Published in: BMC Pregnancy and Childbirth | Issue 1/2019

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Abstract

Background

Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility.

Methods

Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective.

Discussion

This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound.

Trial registration

Dutch Trial Register (NTR5480). Registered 29 October 2015.

Literature
  1. World Health Organization Human Reproduction Programme. WHO statement on caesarean section rates. Sex Reprod Health. 2015;02:1–8 (WHO/RHR/15.02).
  2. Perined: Perinatale Zorg in Nederland 2016. In Utrecht: Perined; 2018.
  3. Naji O, Wynants L, Smith A, Abdallah Y, Saso S, Stalder C, Van Huffel S, Ghaem-Maghami S, Van Calster B, Timmerman D, et al. Does the presence of a caesarean section scar affect implantation site and early pregnancy outcome in women attending an early pregnancy assessment unit? Hum Reprod. 2013;28(6):1489–96.PubMed
  4. Naji O, Wynants L, Smith A, Abdallah Y, Stalder C, Sayasneh A, McIndoe A, Ghaem-Maghami S, Van Huffel S, Van Calster B, et al. Predicting successful vaginal birth after cesarean section using a model based on cesarean scar features examined by transvaginal sonography. Ultrasound Obstet Gynecol. 2013;41(6):672–8.PubMed
  5. Roberge S, Demers S, Berghella V, Chaillet N, Moore L, Bujold E. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis. Am J Obstet Gynecol. 2014;211(5):453–60.PubMed
  6. Hesselman S, Hogberg U, Ekholm-Selling K, Rassjo EB, Jonsson M. The risk of uterine rupture is not increased with single- compared with double-layer closure: a Swedish cohort study. BJOG. 2015;122(11):1535–41.PubMed
  7. Clark EA, Silver RM. Long-term maternal morbidity associated with repeat cesarean delivery. Am J Obstet Gynecol. 2011;205(6 Suppl):S2–10.PubMed
  8. Bij de Vaate AJ, Brolmann HA, van der Voet LF, van der Slikke JW, Veersema S, Huirne JA. Ultrasound evaluation of the cesarean scar: relation between a niche and postmenstrual spotting. Ultrasound Obstet Gynecol. 2011;37(1):93–9.
  9. Bij de Vaate AJ, van der Voet LF, Naji O, Witmer M, Veersema S, Brolmann HA, Bourne T, Huirne JA. Prevalence, potential risk factors for development and symptoms related to the presence of uterine niches following cesarean section: systematic review. Ultrasound Obstet Gynecol. 2014;43(4):372–82.
  10. van der Voet LF, Bij de Vaate AM, Veersema S, Brolmann HA, Huirne JA. Long-term complications of caesarean section. The niche in the scar: a prospective cohort study on niche prevalence and its relation to abnormal uterine bleeding. BJOG. 2014;121(2):236–44.PubMed
  11. Jordans IPM, de Leeuw RA, Stegwee SI, Amso NN, Barri-Soldevila PN, van den Bosch T, Bourne T, Brolmann HAM, Donnez O, Dueholm M, et al. Sonographic examination of uterine niche in non-pregnant women: a modified Delphi procedure. Ultrasound Obstet Gynecol. 2019;53(1):107–15.PubMed
  12. Gurol-Urganci I, Bou-Antoun S, Lim CP, Cromwell DA, Mahmood TA, Templeton A, van der Meulen JH. Impact of caesarean section on subsequent fertility: a systematic review and meta-analysis. Hum Reprod. 2013;28(7):1943–52.PubMed
  13. Vervoort AJ, Uittenbogaard LB, Hehenkamp WJ, Brolmann HA, Mol BW, Huirne JA. Why do niches develop in caesarean uterine scars? Hypotheses on the aetiology of niche development. Hum Reprod. 2015;30(12):2695–702.PubMedPubMed Central
  14. van der Voet LF, Vervoort AJ, Veersema S, Bij de Vaate AJ, Brolmann HA, Huirne JA. Minimally invasive therapy for gynaecological symptoms related to a niche in the caesarean scar: a systematic review. BJOG. 2014;121(2):145–56.
  15. Vervoort A, Vissers J, Hehenkamp WJK, Brolmann HAM, Huirne JAF. The effect of laparoscopic resection of large niches in the uterine caesarean scar on symptoms, ultrasound findings and quality of life: a prospective cohort study. BJOG. 2018;125(3):317–25.
  16. Vervoort AJ, Van der Voet LF, Witmer M, Thurkow AL, Radder CM, van Kesteren PJ, Quartero HW, Kuchenbecker WK, Bongers MY, Geomini PM, et al. The HysNiche trial: hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial. BMC Womens Health. 2015;15:103.PubMedPubMed Central
  17. Nikkels C, Vervoort A, Mol BW, Hehenkamp WJK, Huirne JAF, Brolmann HAM. IDEAL framework in surgical innovation applied on laparoscopic niche repair. Eur J Obstet Gynecol Reprod Biol. 2017;215:247–53.PubMed
  18. Huirne JAF, Vervoort A, Leeuw R, Brolmann HAM, Hehenkamp WJK. Technical aspects of the laparoscopic niche resection, a step-by-step tutorial. Eur J Obstet Gynecol Reprod Biol. 2017;219:106–12.PubMed
  19. Vervoort A, van der Voet LF, Hehenkamp W, Thurkow AL, van Kesteren P, Quartero H, Kuchenbecker W, Bongers M, Geomini P, de Vleeschouwer L, et al. Hysteroscopic resection of a uterine caesarean scar defect (niche) in women with postmenstrual spotting: a randomised controlled trial. BJOG. 2018;125(3):326–34.
  20. Abalos E, Addo V, Brocklehurst P, El Sheikh M, Farrell B, Gray S, Hardy P, Juszczak E, Mathews JE, Masood SN, et al. Caesarean section surgical techniques (CORONIS): a fractional, factorial, unmasked, randomised controlled trial. Lancet. 2013;382(9888):234–48.PubMed
  21. The CAESAR study collaborative group. Caesarean section surgical techniques: a randomised factorial trial (CAESAR). BJOG. 2010;117(11):1366–76.
  22. Di Spiezio Sardo A, Saccone G, McCurdy R, Bujold E, Bifulco G, Berghella V. Risk of cesarean scar defect in single- versus double-layer uterine closure: a systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017;50:578–83.PubMed
  23. Dodd JM, Anderson ER, Gates S, Grivell RM. Surgical techniques for uterine incision and uterine closure at the time of caesarean section. Cochrane Database Syst Rev. 2014;7:CD004732.
  24. Stegwee SI, Jordans I, van der Voet LF, van de Ven PM, Ket J, Lambalk CB, de Groot C, Hehenkamp W, Huirne J. Uterine caesarean closure techniques affect ultrasound findings and maternal outcomes: a systematic review and meta-analysis. BJOG. 2018;125(9):1097–108.PubMed
  25. Osser OV, Jokubkiene L, Valentin L. Cesarean section scar defects: agreement between transvaginal sonographic findings with and without saline contrast enhancement. Ultrasound Obstet Gynecol. 2010;35(1):75–83.PubMed
  26. Aaronson NK, Muller M, Cohen PD, Essink-Bot ML, Fekkes M, Sanderman R, Sprangers MA, te Velde A, Verrips E. Translation, validation, and norming of the Dutch language version of the SF-36 health survey in community and chronic disease populations. J Clin Epidemiol. 1998;51(11):1055–68.PubMed
  27. Dolan P. Modeling valuations for EuroQol health states. Med Care. 1997;35(11):1095–108.PubMed
  28. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199–208.
  29. Ability to Participate in Social Roles and Activities, Short Form 8a [http://​www.​healthmeasures.​net/​explore-measurement-systems/​promis/​intro-to-promis/​list-of-adult-measures].
  30. Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, Ferguson D, D’Agostino R Jr. The female sexual function index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000;26(2):191–208.PubMed
  31. Handleiding iMTA Productivity Cost Questionnaire (iPCQ). [http://​www.​imta.​nl].
  32. Handleiding iMTA Medical Cost Questionnaire (iMCQ). [http://​www.​imta.​nl].
  33. Maarse M, Bij de Vaate AJM, Huirne JAF, Brölmann HAM. De maandkalender, een hulpmiddel voor een efficiënte menstruatieanamnese. Ned Tijdschr Obstet Gynaecol. 2011;124:231–5.
  34. Hakkaart-van Roijen L, van der Linden N, Bouwmans CAM, Kanters TA, Tan SS. Kostenhandleiding: Methodologie van kostenonderzoek en referentieprijzen voor economische evaluaties in de gezondheidszorg. Institute for Medical Technology Assessment; Erasmus Universiteit Rotterdam. Zorginstituut Nederland; 2016.
  35. Lamers LM, Stalmeier PF, McDonnell J, Krabbe PF, van Busschbach JJ. Measuring the quality of life in economic evaluations: the Dutch EQ-5D tariff. Ned Tijdschr Geneeskd. 2005;149(28):1574–8.PubMed
  36. Fenwick E, O'Brien BJ, Briggs A. Cost-effectiveness acceptability curves--facts, fallacies and frequently asked questions. Health Econ. 2004;13(5):405–15.PubMed
  37. Glavind J, Madsen LD, Uldbjerg N, Dueholm M. Ultrasound evaluation of cesarean scar after single- and double-layer uterotomy closure: a cohort study. Ultrasound Obstet Gynecol. 2013;42(2):207–12.PubMed
Metadata
Title
Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development – the 2Close study: a multicentre randomised controlled trial
Authors
S. I. Stegwee
I. P. M. Jordans
L. F. van der Voet
M. Y. Bongers
C. J. M. de Groot
C. B. Lambalk
R. A. de Leeuw
W. J. K. Hehenkamp
P. M. van de Ven
J. E. Bosmans
E. Pajkrt
E. A. Bakkum
C. M. Radder
M. Hemelaar
W. M. van Baal
H. Visser
J. O. E. H. van Laar
H. A. A. M. van Vliet
R. J. P. Rijnders
M. Sueters
C. A. H. Janssen
W. Hermes
A. H. Feitsma
K. Kapiteijn
H. C. J. Scheepers
J. Langenveld
K. de Boer
S. F. P. J. Coppus
D. H. Schippers
A. L. M. Oei
M. Kaplan
D. N. M. Papatsonis
L. H. M. de Vleeschouwer
E. van Beek
M. N. Bekker
A. J. M. Huisjes
W. J. Meijer
K. L. Deurloo
E. M. A. Boormans
H. W. F. van Eijndhoven
J. A. F. Huirne
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2019
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/s12884-019-2221-y

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