The Occlusion RCT

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The Occlusion RCT

• Niels Jørgen Secher
• Copenhagen University Hospital.Hvidovre
• Denmark
• London the 8th of November 2007

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Why is cerclage a common interventiondespite
weak evidence ?
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Conclusion There may be a role for cerclage for
women considered at very high risk (3 or more
pregnancies ending lt 37 weeks).
The MRC/RCO trial 1993 292 women. Uncertain
whether to recommend cervical cerclage

• Delivered before 33 weeks
• 13 in the cerclage group.
• 17 in the control group.
• 24 sutures may prevent one preterm

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Cervical cerclage for prevention of preterm
deliveryMeta-analysis of randomized trials

• Six trials describing a total of 2175 women at
  low or medium risk .
• Pooled results failed to show a reduction in
  preterm delivery before 28 and 34 weeks in women
  assigned to cervical cerclage
• Drakeley et al Obstet Gynecol 2003
  

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Combination of poor obstetric history and
progressively shortening of the cervixAll 19
women delivered after 34 weeks with a cervical
stitch,but only 7 of 16 without a stitch
Althuisius et al Am J Obstet Gynecol 2001
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Strategies for prevention cervical
cerclage     Althuisius S, Van Geijn H. BJOG
200551-6.

• Transvaginal ultrasound follow-up of the cervical
  length with secondary intervention, if necessary.
  Appears to be a safe alternative to traditional
  cervical cerclage (prevents 50 unnecessary
  interventions)
• Secondary and tertiary cerclage if indicated.

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Abdominal versus vaginal cerclage after a failed
transvaginal cerclage.

• 117 woman had a subsequent transabdominal
  cerclage
• 40 women had a subsequent transvaginal cerclage
• The likelihood of perinatal death or delivery
  before 24 weeks was 6,0 (3,8-8,2)after
  transabdominal cerclage and 12,5(2,7-22,7)after
  transvaginal cerclage.
• Zaveri et al Am J Obstet Gynecol 2002

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If there are no benefits from cerclage, it could
be because

• They do not work
• Incorrect insertion techniques are used
• Selection of patients is incorrect
• The cervix is so weak that it cannot be corrected
  with a suture
• Failure of the protective mechanism of the
  cervical plug, possibly due to ascending genital
  infections

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Cervical cerclage

• Shirodkar 1955 (Lash et Lash 1950)
• Mc Donald 1957
• Abdominal (Benson et Durfee) 1965
• Total Cervical occlusion (Prof. Saling 1984)
• Shirodkar and lower cervical occlusion (Prof.
  P. Steer 2002)
• Mc Donald and lower cervical occlusion (McCormack
  and NJ Secher 2003)

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Cervical cerclage

• Shirodkar 1955 (Lash et Lash 1950)
• Mc Donald 1957
• Abdominal (Benson et Durfee) 1965
• Total Cervical occlusion (Prof.Saling 1984)
• Shirodkar and lower cervical occlusion (Prof.
  P. Steer 2002)
• Mc Donald and lower cervical occlusion
  (McCormack and NJ Secher 2003)

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Total cervical occlusionProfessor Saling 1997

• All clinics 659 of 819 80 livebirth with
  occlusion.
• 26 livebirth without occlusion
• not randomised

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Cervical cerclage

• Shirodkar 1955 (Lash et Lash 1950)
• Mc Donald 1957
• Abdominal (Benson et Durfee) 1965
• Total Cervical occlusion Prof.Saling 1984
• Shirodkar and lower cervical occlusion Prof. P.
  Steer 2002
• Mc Donald and lower cervical occlusion Riaydh
  2003 McCormack and NJ Secher

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My experience of cervical sutures

• 92,5 OF 53 WOMAN HAD PREGNANCY BEYOND 30 WEEKS
• rfr

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CERVICAL SUTURES CHELSEA AND WESTMINSTER

• 53 pregnancies
• 19 McDonald
• 22 Shirodkar
• 12 Abdominal
• 49 babies survived, all intact - 92 success rate
• All had occlusion suture in addition to primary
  suture

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PRINCIPLE OF SHIRODKAR/ABDOMINAL SUTURE PLUS
OCCLUSION SUTURE
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OCCLUSION SUTURE
P. J. Steer
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Dee McCormack
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Rikke Helmig Merete Hein
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Intrauterine infection
Positive culture from amniotic fluid

• 30 of patients with PPROM

• 20 of patients with preterm labor and intact
  membranes

• 25 - 50 of patients presenting a cervical
  dilatation
• of gt 2 cm in the second trimester

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Cervical insufficiency
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Two-dimensional ultrasound image showing amniotic
fluid sludge in a patient with a short cervix
and a cervical funnel.
Romero R et al. What is amniotic fluid
'sludge'?Ultrasound Obstet Gynecol. 2007
Oct30(5)793-8
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The cervical mucus plugDoes it exist?
What a silly question!
The midwife
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Cervical mucous plug
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The cervical mucus plug
Cervical mucus plug 11 weeks of gestation
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The cervical mucus plug
Cervical mucus plug at term
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The cervical mucus plug
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Data on cervical mucus plugs

• The mass was
• 3.7 gram range (1.7-6.1)
• It is a viscous, sticky, opaque and gelatinous
  structure

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An in vitro study of antibacterial properties of
the cervical mucus plug
Agar overlay assay
Agar plate with imbedded bacterial strain

• Streptococcus pyogenes
• Streptococcus agalactia
• Enterococcus faecium
• Staphylococcus aureus
• Staphylococcus saprofyticus
• E. coli
• Pseudomonas aeroginosa
• hein and helwig

Filter
Cervical mucus plug
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Cervical Plug

• Calprotectin, Lactoferrin
• Protease inhibitor, lysocyme, defensine
• High immunoglobulin level
• Phagocytose
• Conclusion
• Gate keeper for ascending infection.

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Cervical cerclage

• Shirodkar 1955 (Lash et Lash 1950)
• Mc Donald 1957
• Abdominal (Benson et Durfee) 1965
• Total Cervical occlusion Prof.Saling 1984
• Shirodkar and lower cervical occlusion Prof. P.
  Steer 2002
• Mc Donald and lower cervical occlusion Riaydh
  2003 McCormack and NJ Secher

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Cervical occlusion

• McDonald suture
• Closure of the external os with nylon.
• Does this procedure protect the plug and prevent
  ascending infection.

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Double cerclage
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Cervical occlusion
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Cervical occlusion
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Results the Riaydh study
34 women

• Before cervical occlusion
• Total live 20/159
• 13
• Failure 87

• After cervical occlusion
• Total live 30/34
• 88
• Failure 12

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Single versus double cerclage

• The outcomes of all patients in the original
  group who had previously had at least one
  cerclage were investigated. (41 single sutures)
• These results were compared with their own
  outcomes in the occlusion group. (24 occlusion
  sutures)

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Single vs. Double
24 women

• Single N41
• Live births 14/41 34,2
• Survival Overall - 8/41 20

• Double N24
• Live births 20/24 83,3
• Survival Overall 20/24 83

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Conclusions

• Following the occlusion suture, pregnancy outcome
  was unusually favourable
• Cervical occlusion suture deserves evaluation by
  a prospective, randomised trial

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Randomized controlled Trial

• Cervical occlusion in women with cervical
  insufficiency protocol for a randomised,
  controlled trial with cerclage, with and without
  cervical occlusion
• Authors Secher McCormack Weber Hein Helmig
• Source BJOG An International Journal of
  Obstetrics Gynaecology, Volume 114, Number 5,
  May 2007 , pp. 649-e6(-648)

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Website

• www.cervicalocclusion.com
• Website with information regarding the Trial,
  including consent forms and information sheets.

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cerclage

• Profylactical/primary prevention
• Therapeutical /secondary cerclage without
  membranes exposed to the vagina
• Therapeutical /tertiary cerclage with membranes
  exposed to the vagina

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Cerclage Nomenclature
New Nomenclature History-indicated Ultrasound-indi
cated Physical examination - indicated
Old Nomenclature Prophylactic, elective Therapeuti
c, salvage Rescue, emergency, urgent
Berghella et al 2007
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Methods

• The women will be randomised between a single
  (vaginal or abdominal) and a double cerclage.
  The cervical cerclage (Mc Donald or Shirodkar)
  as well as the abdominal suture will be done with
  the same material and technique normally used by
  the participating department. Those randomised
  to the double cerclage will have their external
  os closed with a continuous nylon 2-0 / 3-0
  suture, in addition to the standard single
  cerclage. Local guidelines concerning
  antibiotics, Heparin, bed rest, tocolytics etc.
  are followed and recorded in the follow-up form.

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Prophylactic study

• History of cervical incompetence / insufficiency.
  (Delivery 15 - lt 36 weeks)
• Congenital short cervix (secondary to maternal
  administration of diethyl stilbestrol, DES) or
  traumatic/surgical damage rendering the vaginal
  approach difficult (e.g. conisation)
• Cervical suture applied in previous pregnancy,
  successful outcome
• Previous failed cerclage

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Therapeutic study

• 5) Secondary cerclage Short cervix, without the
  membranes being exposed to the vagina.
• 6) Tertiary cerclage Short cervix, membranes
  exposed to the vagina
•  
• Observational study Eligible women who refuse to
  be randomised will participate in an
  observational study.
• 7) Repeat / Requested Cervical Occlusion

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Flow chart for the cerclage trial

Women eligible for inclusion in the trial
Appropiate trial arm for the patient
The therapeutical trial arm The prophylactic
trial arm
Randomisation regime
 
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Steering Committee To approve the
core protecol To approve Changes
To receive
report from DMC
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The Monitoring Committee

• Philip Steer. London
• Trine B Henriksen. Aarhus DK
• Jakob Hjort. Aarhus DK

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Assuming that the preterm delivery rate in the
non-occlusive group are 25, and we expect a
reduction in preterm delivery rate of at least
50.Only 200 woman would have to be
randomized, to prove beyond a reasonable doubt
that cervical occlusion is the treatment of
choice for these women.






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Enrolment in The Cerclage Trial per October
3rd
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Low budget 21.000 We apply for further
funding
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Contacts

• njsecher_at_dadlnet.dk
• deemccormack_at_hotmail.com
• Thank you ?