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C H A P T E R 2Prevalence, potential risk factors for development and symptoms

related to the presence of uterine niches following Cesarean section:

systematic review

A.J.M. Bij de Vaate

L.F. van der Voet

O. Naji

M. Witmer

S. Veersema

H.A.M. Brölmann

T. Bourne

J.A.F. Huirne

Ultrasound in Obstetrics & Gynecology 2014;43(4):372-82


20

C h a p t e r 2

Abstract

ObjectiveTo review systematically the medical literature reporting on the prevalence of a niche at

the site of a Cesarean section (CS) scar using various diagnostic methods, on potential risk

factors for the development of a niche and on niche-related gynecological symptoms in

non-pregnant women.

MethodsThe PubMed and EMBASE databases were searched. All types of clinical study reporting

on the prevalence, risk factors and/or symptoms of a niche in non-pregnant women with

a history of CS were included, apart from case reports and case series.

ResultsTwenty-one papers were selected for inclusion in the review. A wide range in the prevalence

of a niche was found. Using contrast-enhanced sonohysterography in a random population

of women with a history of CS, the prevalence was found to vary between 56% and 84%.

Nine studies reported on risk factors and each study evaluated different factors, which

made it difficult to compare studies. Risk factors could be classified into four categories:

those related to closure technique, to development of the lower uterine segment or location

of the incision or to wound healing, and miscellaneous factors. Probable risk factors are

single-layer myometrium closure, multiple CSs and uterine retroflexion. Six out of eight

studies that evaluated niche-related symptoms described an association between the

presence of a niche and postmenstrual spotting.

ConclusionsThe reported prevalence of a niche in non-pregnant women varies depending on the method

of detection, the criteria used to define a niche and the study population. Potential risk

factors can be categorized into four main categories, which may be useful for future

research and meta-analyses. The predominant symptom associated with a niche is

postmenstrual spotting.


21

Prevalence, risk factors and symptoms

Introduction

In recent decades, the percentage of Cesarean section (CS) deliveries has dramatically

increased in most developed countries. An average rate of 21.1% for developed countries

has been reported, with a range between 6.2% and 36%.1 There are some well-known

complications, such as uterine rupture and pathologically adherent placenta in future

pregnancy2,3, but there is now an increasing interest in the long-term effects of this

procedure. Recently, the presence of a niche at the site of a CS scar has been observed.4-7

A niche is mainly a sonographic finding and has been defined as a triangular anechoic area

at the presumed site of incision.8 However, a generally accepted definition of a niche is

still under debate. Alternative terms for a niche are Cesarean scar defect4,9,10, deficient

Cesarean scar11, diverticulum12, pouch6 and isthmocele.13 Interest in the potential clinical

relevance of a niche has increased in the last few years and a growing number of studies

on the subject have been published. Various methods to detect and measure a niche have

been described. The majority of papers have evaluated the niche with the use of transvaginal

sonography (TVS)5,9-11,14,15 and contrast-enhanced sonohysterography (SHG)5,8,15-18, but a

minority have used hysteroscopy6,13,16 or hysterosalpingography.12 At present there is no

consensus regarding the gold standard for the detection and measurement of a niche. As

not all women with a history of CS develop a niche, it is of interest to identify the risk

factors that may predict their development. In addition, there is growing interest in possible

associations between the presence of a niche and various gynecological symptoms, and

in the mechanisms behind the development of these symptoms. A common symptom

reported to be associated with the presence of a niche is postmenstrual spotting.5,6,10,18

The objective of the current review was to give a systematic overview of the available

literature on the prevalence of a niche using various diagnostic methods, on potential risk

factors for the development of a niche and on niche-related gynecological symptoms in

non-pregnant women.

Methods

Search strategyIn February 2013, we searched the PubMed and EMBASE databases for words in the title

or abstract and MeSH terms. All possible combinations of known terms for niche (cicatrix,

scar, isthmocele, anechoic, pouch, wound dehiscence, diverticulum), uterus (uterine

diseases, myometrium, endometrium, myoendometrium) and CS (Cesarean, caesarean,

c section, abdominal delivery, postCesarean, postcaesarean) were used. The complete

electronic search strategy is provided in Appendix S1. Reference lists of the studies were

cross-checked to identify cited articles not captured by the electronic search.


22

C h a p t e r 2

Study selection criteriaWe included all types of clinical study reporting on the prevalence, risk factors and/or

symptoms of a niche in non-pregnant women, using TVS, SHG or hysteroscopy. Studies

in the English language published as full papers in peer-reviewed journals were included.

Case reports or small case series were excluded. Given the limited number of cohort

studies or randomized controlled trials, we did not apply additional methodological filters

for paper selection. The types of study we expected to find were randomized controlled

trials, prospective cohort studies (following a group of similar individuals over time),

retrospective cohort studies (comparison of patients’ medical records for a particular

outcome), cross-sectional studies (observation of a population at one specific point in time)

and case–control studies (comparing subjects who have a certain condition with patients

who do not, in order to identify a factor that may contribute to this condition). Studies were

selected in a two-stage process by two researchers (J.H. and A.B.). First, eligibility was

assessed based on the titles and abstracts. Full manuscripts were obtained for all selected

studies. In the second step, the decision for final inclusion was made after examination of

the full papers. The outcomes of this review are the prevalence of a niche in women with

a history of CS, risk factors for the development of a niche and symptoms related to the

presence of a niche.

Presentation of dataThe PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)

statement was used for reporting the methods, results and discussion sections of the

current review and the STROBE (Strengthening the Reporting of Observational Studies in

Epidemiology) statement was used to obtain an impression of the quality of the included

studies.19,20 Included papers were ordered in the tables according to the outcome of the

most relevant items of the STROBE checklist, such as clear definition of the study

population and clear description of the method of evaluation. The extended STROBE

checklist, including all STROBE items, is provided in Appendix S2. The QUADAS (Quality

Assessment of Diagnostic Accuracy) checklist was used for assessing the methodological

quality of the studies reporting on the accuracy of diagnostic tests.21 The included studies

were divided into papers reporting on niche prevalence, risk factors and symptoms. The

tables were subdivided into two sections: a section with studies performed in a random

population of women with a history of CS, and a section with studies performed in a

population of women with gynecological symptoms. All studies were assessed for potential

risk of bias. Papers were ranked based on methodological criteria, which means that

randomized controlled trials and studies with a clear definition of study population and

method of evaluation were placed at the top of the tables. In the table reporting on risk

factors, studies including women with one previous CS and in which multivariate analysis

was used were placed in the first few columns.


23


Results

Literature identificationThe electronic search in PubMed and EMBASE generated 2953 records. Four additional

records were identified through cross-checking. After screening 2957 abstracts, 27 papers

were thought to meet the inclusion criteria and were selected for full assessment. Six

papers were excluded for the following reasons: study design (two case reports), three

publications did not meet the outcome measures and in one study women were examined

at 14–16 weeks’ gestation. We included two studies that were subgroups of a study by

Vikhareva Osser et al.9 as new outcome parameters were tested.17,22 The final study

included 21 papers (Figure 1).

The niche was evaluated in a random population of women with a history of CS in 12

studies.4,5,7,9,14,15,17,22-26 In these studies, women with a history of CS were included regardless

of the presence of symptoms. The other nine studies evaluated women who were referred

for a variety of gynecological symptoms, such as abnormal uterine bleeding or

infertility.6,8,10,11,13,16,18,27,28 The included studies with a random population and those with a

population of women with symptoms are reported in Table 1. The diagnostic methods used

for evaluation of the uterine cavity were TVS in 16 studies4-6,9-11,14,15,17,22-28, SHG in eight

studies5,7,8,15-18,22 and hysteroscopy in four studies.6,13,16,23

Figure 1 Flow diagram of literature search for articles on uterine niches following Cesarean section.


24

C h a p t e r 2

PrevalenceThe prevalence of a niche was reported in 15 papers. Seven studies were performed in a

random population of women with a history of CS (Table 2) and eight in a population of

women with gynecological symptoms (Table 3).

Using TVS, the reported prevalence of a niche varied between 24% and 70% in four studies

with a random population of women with a history of one or multiple CSs.4,5,9,17 All four

studies met the STROBE criteria in terms of a clear description of study population and

method of evaluation. Using SHG, the prevalence of a niche varied between 56% and 84%

in three studies with a random population that met the STROBE criteria.5,15,17

The prevalence of a niche as ascertained by hysteroscopy was only evaluated in populations

of women with gynecological symptoms.13,16 (Table 3) Two studies meeting the STROBE

criteria and conducted in a random population of women with a history of CS reported the

prevalence of a niche using both TVS and SHG.5,17 Vikhareva Osser et al.17 reported a niche

prevalence of 84% with SHG and 70% with TVS, with a niche defined as any indentation

or other defect in the scar. The same authors found that the length and height of Cesarean

scar defects were greater when evaluated using SHG than when evaluated using TVS, and

that more scars were seen and classified subjectively as large by SHG without a change

being noted in the shape. Bij de Vaate et al.5 found a niche prevalence of 56% with SHG

and 24% with TVS, and defined a niche as an anechoic area at the site of the CS scar with

a depth of at least 1 mm.

Another study performed in women with gynecological symptoms compared the accuracy

of SHG with hysteroscopy as the reference technique and demonstrated that SHG is

comparable to hysteroscopy for the diagnosis of a niche as shown by the sensitivity (87%),

specificity (100%), positive predictive value (100%), negative predictive value (95%) and

overall accuracy (96%).16 This study did not meet two criteria of the QUADAS checklist.21

First, the study population consisted of women with gynecological symptoms. Second,

the hysteroscopy findings were interpreted with prior knowledge of the SHG results.

Another study reported that hysteroscopy as the reference technique showed 100%

correlation with TVS in the detection of a niche.6 However, this study did not meet the

QUADAS criteria either, as it was a retrospective study in women with a niche assessed

using TVS, and hysteroscopy was performed in a subgroup of women who wanted to

become pregnant (verification bias).

Niche shapeFive studies reporting on niche shape evaluated the shape in the sagittal plane with TVS

or SHG.5,6,9,14,17 Most authors described the niche as being triangular in shape with TVS.6,9,14

Vikhareva Osser et al.9 reported that 83% of niches were triangular, 2% were round, 4%

were oval and 10% showed no remaining myometrium over the defect. The same group

demonstrated that the shape did not change when evaluated by SHG.17 Another study

demonstrated that the niche was visualized as a triangular anechoic area in all women.6 In

addition, it was reported that a wedge defect was present in 21% of women with a history

of CS, inward protrusion (internal surface of the scar bulging toward the uterine cavity) in


25


6%, outward protrusion (external surface bulging toward the bladder or abdominal cavity)

in 15%, hematoma (echogenic mass adjacent to the wound site of the anterior wall of the

lower uterine segment) in 4% and inward retraction (external surface of the scar dimpled

toward the myometrial layer) in 4%.14 Bij de Vaate et al.5, using SHG, found that 50% of

niches were semicircular, 32% were triangular and 10% were droplet-shape; inclusion

cysts accounted for 7%.If we consider only the methodologically well-performed studies

according to the STROBE criteria with a random population of women with a history of CS,

triangular and semicircular are found to be the most commonly described shapes.5,9

Table 1 Methodological characteristicsBased on the STROBE-statement, of included studies performed either in a random population of women with a history of Cesarean section (CS) or in women with a history of CS and gynecological symptoms (i.e. subject to selection bias)

Study Design Cle

ar d

efin

itio

n

of

stu

dy

po

pu

lati

on

Cle

ar d

escr

ipti

on

o

f n

ich

e as

sess

men

t

Cle

ar d

escr

ipti

on

o

f as

sess

men

t o

f al

l ou

tco

mes

Des

crip

tio

n o

f m

issi

ng

dat

a

Co

rrec

tio

n f

or

con

fou

nd

ers

Random population

Yazicioglu, 200626 RCT Yes Yes No Yes Yes

Vikhareva Osser, 201022 Prosp. cohort Yes Yes Yes NA Yes

Bij de Vaate, 20115 Prosp. cohort Yes Yes Yes Yes Yes

Hayakawa, 200625 Prosp. cohort Yes Yes Yes NA Yes

Valenzano, 200615 Case-control Yes Yes Yes NA No

Vikhareva Osser, 201017 Prosp. cohort Yes Yes Yes NA No

Vikhareva Osser, 20099 Case-control Yes Yes Yes NA No

Ceci, 201223 Prosp. cohort Yes Yes Yes Yes No

Armstrong, 20034 Case-control Yes Yes Yes NA No

Regnard, 20047 Prosp. cohort No Yes Yes NA No

Chen, 199014 Prosp. cohort No No No NA No

Glavind, 201224 Retro. cohort Yes Yes Yes NA No

Women with gynecological symptoms

Ofili-Yebovi, 200811 Prosp. cohort Yes Yes Yes Yes Yes

El-Mazny, 201116 Cross-sectional Yes Yes Yes NA No

Monteagudo, 20018 Prosp. cohort Yes Yes Yes NA No

Wang, 200910 Cross-sectional No Yes Yes NA Yes

Chang, 200927 Prosp. cohort No Yes No NA No

Uppal, 201128 Prosp. cohort No No Yes No Yes

Borges, 201013 Prosp. cohort No No No NA No

Thurmond, 199918 Prosp. cohort No No No NA No

Fabres, 20036 Retro. cohort No Yes No NA No

Only first author is listed for each study. Prosp., prospective; RCT, randomized controlled trial; Retro., retrospective.


26

C h a p t e r 2

Tabl

e 2

Pre

vale

nce

of a

nic

he in

rela

tion

to d

iagn

osti

c m

etho

d in

a ra

ndom

pop

ulat

ion

of w

omen

wit

h a

hist

ory

of C

esar

ean

sect

ion

(CS

)

Stu

dy

Des

ign

NP

op

ula

tio

nD

efin

itio

n o

f a

nic

he

Ou

tco

me

Nic

he

pre

vale

nce

o

n T

VS

(%

)

Nic

he

pre

vale

nce

o

n S

HG

(%

)R

esu

lts

Pop

ulat

ion

with

his

tory

of

only

one

CS

Vale

nzan

o,

2006

15

Cas

e-co

ntro

l 11

6 w

ith

prev

ious

CS

(n=

217)

Ran

dom

sel

ectio

n of

w

omen

with

firs

t de

liver

y be

twee

n 19

95 a

nd 2

004:

va

gina

l birt

h (n

=10

1) o

r C

S

(n=

116)

Tria

ngul

ar, a

nech

oic

area

at

pres

umed

site

of

inci

sion

Pre

vale

nce

of

mor

phol

ogic

al c

hang

es o

f LU

S, o

n TV

S o

r S

HG

60%

Nic

he p

reva

lenc

e si

mila

r in

w

omen

who

had

un

derg

one

CS

at

3-12

m

onth

s, 1

-5 y

ears

and

5-

10 y

ears

aft

er C

S

Pop

ulat

ion

with

his

tory

of

one

or m

ultip

le C

Ss

Bij

de V

aate

, 20

115

Pro

sp. c

ohor

t22

5C

onse

cutiv

e in

clus

ion

6-12

m

onth

s af

ter

CS

Ane

choi

c ar

ea a

t si

te o

f C

S

scar

with

dep

th o

f at

leas

t 1

mm

Pre

vale

nce,

dep

th a

nd

volu

me

of n

iche

on

TVS

an

d S

HG

, and

son

ogra

phic

cl

assi

ficat

ion

(SH

G) b

ased

on

sha

pe

24%

56%

Mos

t co

mm

on s

hape

s se

mic

ircul

ar (5

0.4%

), tr

iang

ular

(31.

6%),

drop

let-

shap

ed (1

0.3%

) an

d in

clus

ion

cyst

s (6

.8%

)

Vik

hare

va

Oss

er, 2

01017

*P

rosp

. coh

ort

108

His

tory

of

CS

in p

rece

ding

6-

9 m

onth

s, w

ho h

ad

unde

rgon

e TV

S a

nd S

HG

Any

vis

ible

def

ect

or

inde

ntat

ion

in s

car,

how

ever

sm

all

Agr

eem

ent

betw

een

TVS

an

d S

HG

with

reg

ard

to

prev

alen

ce, l

engt

h, h

eigh

t

and

shap

e of

nic

he

70%

†84

%†

Mos

t sc

ar d

efec

ts

tria

ngul

ar in

sha

pe. S

hape

di

d no

t ch

ange

at

SH

G, b

ut

was

eas

ier

to d

elin

eate

bo

rder

s of

sca

r de

fect

; pr

eval

ence

of

(larg

e)

nich

es h

ighe

r on

SH

G.

Vik

hare

va

Oss

er, 2

0099

Cas

e-co

ntro

l 16

2 w

ith

prev

ious

CS

(n=

287)

Del

iver

ed 6

-9 m

onth

s be

fore

exa

min

atio

n:

prim

ipar

ae w

ith

unco

mpl

icat

ed v

agin

al

deliv

ery

(n=

125)

or

wom

en

deliv

ered

by

CS

at

leas

t on

ce (n

=16

2).

Any

vis

ible

def

ect

or

inde

ntat

ion

in s

car,

how

ever

sm

all

Pre

vale

nce,

siz

e, s

hape

an

d lo

catio

n of

CS

sca

r de

fect

s on

TV

S

69%

Mos

t sc

ar d

efec

ts

tria

ngul

ar in

sha

pe (8

3%),

som

e ro

und

(2%

) or

oval

(4

%),

and

10%

tot

al

defe

cts;

sca

rs w

ith d

efec

ts

loca

ted

low

er in

ute

rus

than

inta

ct s

cars

Tabl

e 2

Con

tinue

d

Arm

stro

ng,

2003

4

Cas

e-co

ntro

l32

with

pre

viou

s C

S (n

=70

)Vo

lunt

eers

age

d 18

-40

with

his

tory

of

vagi

nal

(n=

38) o

r ce

sare

an (n

=32

) de

liver

y w

ithin

pre

cedi

ng 5

ye

ars

Son

ogra

phic

de

mon

stra

tion

of f

luid

w

ithin

CS

sca

r

Pre

vale

nce

of C

S s

car

defe

cts

on T

VS

42%

Reg

nard

, 20

047

Pro

sp. c

ohor

t 33

His

tory

of

CS

pla

nnin

g a

furt

her

preg

nanc

yTr

iang

ular

, ane

choi

c ar

ea a

t pr

esum

ed s

ite o

f in

cisi

on

Pre

vale

nce

of n

iche

and

fr

eque

ncy

of d

ehis

cenc

e at

si

te o

f ut

erin

e sc

ar o

n S

HG

58%

6% p

reva

lenc

e of

sca

r de

hisc

ence

(dep

th o

f ni

che

at le

ast

80%

of

ante

rior

myo

met

rium

)

Che

n, 1

99014

‡

Pro

sp. c

ohor

t 47

His

tory

of

CS

, per

form

ed

betw

een

7 da

ys a

nd 8

ye

ars

prev

ious

ly

Vario

us p

atte

rns

of C

S s

car

defin

ed

Eva

luat

ion

of L

US

on

TVS

49%

sho

wed

nor

mal

pa

tter

ns, 2

1% w

edge

de

fect

, 15%

out

war

d pr

otru

sion

, 6%

inw

ard

prot

rusi

on, 4

% h

emat

oma

and

4% in

war

d re

trac

tion

Onl

y fir

st a

utho

r is

list

ed f

or e

ach

stud

y. *

Sub

grou

p an

alys

is o

f V

ikha

reva

Oss

er9 .

†W

omen

who

had

und

ergo

ne o

ne o

r tw

o C

Ss.

‡P

regn

ant

wom

en in

the

stu

dy p

opul

atio

n w

ere

excl

uded

fro

m t

his

revi

ew. L

US

, low

er u

terin

e se

gmen

t; P

rosp

., pr

ospe

ctiv

e; S

HG

, con

tras

t-en

hanc

ed s

onoh

yste

rogr

aphy

; TV

S=

tran

svag

inal

son

ogra

phy.


27


Tabl

e 2

Pre

vale

nce

of a

nic

he in

rela

tion

to d

iagn

osti

c m

etho

d in

a ra

ndom

pop

ulat

ion

of w

omen

wit

h a

hist

ory

of C

esar

ean

sect

ion

(CS

)

Stu

dy

Des

ign

NP

op

ula

tio

nD

efin

itio

n o

f a

nic

he

Ou

tco

me

Nic

he

pre

vale

nce

o

n T

VS

(%

)

Nic

he

pre

vale

nce

o

n S

HG

(%

)R

esu

lts

Pop

ulat

ion

with

his

tory

of

only

one

CS

Vale

nzan

o,

2006

15

Cas

e-co

ntro

l 11

6 w

ith

prev

ious

CS

(n=

217)

Ran

dom

sel

ectio

n of

w

omen

with

firs

t de

liver

y be

twee

n 19

95 a

nd 2

004:

va

gina

l birt

h (n

=10

1) o

r C

S

(n=

116)

Tria

ngul

ar, a

nech

oic

area

at

pres

umed

site

of

inci

sion

Pre

vale

nce

of

mor

phol

ogic

al c

hang

es o

f LU

S, o

n TV

S o

r S

HG

60%

Nic

he p

reva

lenc

e si

mila

r in

w

omen

who

had

un

derg

one

CS

at

3-12

m

onth

s, 1

-5 y

ears

and

5-

10 y

ears

aft

er C

S

Pop

ulat

ion

with

his

tory

of

one

or m

ultip

le C

Ss

Bij

de V

aate

, 20

115

Pro

sp. c

ohor

t22

5C

onse

cutiv

e in

clus

ion

6-12

m

onth

s af

ter

CS

Ane

choi

c ar

ea a

t si

te o

f C

S

scar

with

dep

th o

f at

leas

t 1

mm

Pre

vale

nce,

dep

th a

nd

volu

me

of n

iche

on

TVS

an

d S

HG

, and

son

ogra

phic

cl

assi

ficat

ion

(SH

G) b

ased

on

sha

pe

24%

56%

Mos

t co

mm

on s

hape

s se

mic

ircul

ar (5

0.4%

), tr

iang

ular

(31.

6%),

drop

let-

shap

ed (1

0.3%

) an

d in

clus

ion

cyst

s (6

.8%

)

Vik

hare

va

Oss

er, 2

01017

*P

rosp

. coh

ort

108

His

tory

of

CS

in p

rece

ding

6-

9 m

onth

s, w

ho h

ad

unde

rgon

e TV

S a

nd S

HG

Any

vis

ible

def

ect

or

inde

ntat

ion

in s

car,

how

ever

sm

all

Agr

eem

ent

betw

een

TVS

an

d S

HG

with

reg

ard

to

prev

alen

ce, l

engt

h, h

eigh

t

and

shap

e of

nic

he

70%

†84

%†

Mos

t sc

ar d

efec

ts

tria

ngul

ar in

sha

pe. S

hape

di

d no

t ch

ange

at

SH

G, b

ut

was

eas

ier

to d

elin

eate

bo

rder

s of

sca

r de

fect

; pr

eval

ence

of

(larg

e)

nich

es h

ighe

r on

SH

G.

Vik

hare

va

Oss

er, 2

0099

Cas

e-co

ntro

l 16

2 w

ith

prev

ious

CS

(n=

287)

Del

iver

ed 6

-9 m

onth

s be

fore

exa

min

atio

n:

prim

ipar

ae w

ith

unco

mpl

icat

ed v

agin

al

deliv

ery

(n=

125)

or

wom

en

deliv

ered

by

CS

at

leas

t on

ce (n

=16

2).

Any

vis

ible

def

ect

or

inde

ntat

ion

in s

car,

how

ever

sm

all

Pre

vale

nce,

siz

e, s

hape

an

d lo

catio

n of

CS

sca

r de

fect

s on

TV

S

69%

Mos

t sc

ar d

efec

ts

tria

ngul

ar in

sha

pe (8

3%),

som

e ro

und

(2%

) or

oval

(4

%),

and

10%

tot

al

defe

cts;

sca

rs w

ith d

efec

ts

loca

ted

low

er in

ute

rus

than

inta

ct s

cars

Tabl

e 2

Con

tinue

d

Arm

stro

ng,

2003

4

Cas

e-co

ntro

l32

with

pre

viou

s C

S (n

=70

)Vo

lunt

eers

age

d 18

-40

with

his

tory

of

vagi

nal

(n=

38) o

r ce

sare

an (n

=32

) de

liver

y w

ithin

pre

cedi

ng 5

ye

ars

Son

ogra

phic

de

mon

stra

tion

of f

luid

w

ithin

CS

sca

r

Pre

vale

nce

of C

S s

car

defe

cts

on T

VS

42%

Reg

nard

, 20

047

Pro

sp. c

ohor

t 33

His

tory

of

CS

pla

nnin

g a

furt

her

preg

nanc

yTr

iang

ular

, ane

choi

c ar

ea a

t pr

esum

ed s

ite o

f in

cisi

on

Pre

vale

nce

of n

iche

and

fr

eque

ncy

of d

ehis

cenc

e at

si

te o

f ut

erin

e sc

ar o

n S

HG

58%

6% p

reva

lenc

e of

sca

r de

hisc

ence

(dep

th o

f ni

che

at le

ast

80%

of

ante

rior

myo

met

rium

)

Che

n, 1

99014

‡

Pro

sp. c

ohor

t 47

His

tory

of

CS

, per

form

ed

betw

een

7 da

ys a

nd 8

ye

ars

prev

ious

ly

Vario

us p

atte

rns

of C

S s

car

defin

ed

Eva

luat

ion

of L

US

on

TVS

49%

sho

wed

nor

mal

pa

tter

ns, 2

1% w

edge

de

fect

, 15%

out

war

d pr

otru

sion

, 6%

inw

ard

prot

rusi

on, 4

% h

emat

oma

and

4% in

war

d re

trac

tion

Onl

y fir

st a

utho

r is

list

ed f

or e

ach

stud

y. *

Sub

grou

p an

alys

is o

f V

ikha

reva

Oss

er9 .

†W

omen

who

had

und

ergo

ne o

ne o

r tw

o C

Ss.

‡P

regn

ant

wom

en in

the

stu

dy p

opul

atio

n w

ere

excl

uded

fro

m t

his

revi

ew. L

US

, low

er u

terin

e se

gmen

t; P

rosp

., pr

ospe

ctiv

e; S

HG

, con

tras

t-en

hanc

ed s

onoh

yste

rogr

aphy

; TV

S=

tran

svag

inal

son

ogra

phy.


28

C h a p t e r 2

Tabl

e 3

Pre

vale

nce

of a

nic

he in

rela

tion

to d

iagn

osti

c m

etho

d in

a p

opul

atio

n of

wom

en w

ith

a hi

stor

y of

Ces

area

n se

ctio

n (C

S) a

nd g

ynec

olog

ical

sym

ptom

s (i

.e. s

ubje

ct to

sel

ecti

on b

ias)

Stu

dy

Des

ign

NP

op

ula

tio

nD

efin

itio

n o

f a

nic

he

Ou

tco

me

Nic

he

pre

vale

nce

o

n T

VS

(%

)

Nic

he

pre

vale

nce

o

n S

HG

(%

)

Nic

he

pre

vale

nce

o

n H

S (

%)

Res

ult

s

Pop

ulat

ion

unde

rgoi

ng g

ynec

olog

ical

ultr

asou

nd f

or a

var

iety

of

indi

catio

ns, w

ith h

isto

ry o

f on

e or

mul

tiple

CS

s

Ofil

i-Yeb

ovi,

2008

11

Pro

sp. c

ohor

t 32

4H

isto

ry o

f tr

ansv

erse

lo

wer

-seg

men

t C

S,

refe

rred

for

var

iety

of

gyne

colo

gica

l ind

icat

ions

Any

det

ecta

ble

thin

ning

of

myo

met

rium

at

site

of

CS

sca

r

Pre

vale

nce

of C

S s

car

defe

cts

and

desc

riptio

n of

m

orph

olog

ical

fea

ture

s on

TV

S

19%

Sca

r de

fect

sev

ere

(≥50

%

of d

epth

of

myo

met

rium

) in

10%

El-M

azny

, 20

1116

Cro

ss-s

ectio

nal

75H

isto

ry o

f C

S in

pr

eced

ing

1-5

year

s,

exam

ined

for

infe

rtili

ty,

men

stru

al d

isor

ders

or

recu

rren

t pr

egna

ncy

loss

Filli

ng d

efec

t in

CS

sca

r, de

fined

as

tria

ngul

ar,

anec

hoic

are

a at

pr

esum

ed s

ite o

f in

cisi

on

Acc

urac

y of

SH

G v

ersu

s go

ld s

tand

ard

HS

for

dete

ctio

n of

nic

he a

nd

thic

knes

s of

sca

r

27%

31%

SH

G c

ompa

rabl

e to

HS

as

show

n by

sen

s. (8

7%),

spec

. (10

0%),

PP

V

(100

%),

NP

V (9

5%) a

nd

over

all a

ccur

acy

(96%

) in

diag

nosi

s of

nic

he; s

car

thic

knes

s lo

wer

at

SH

G

than

at

HS

(P=

0.01

6)

Mon

teag

udo,

20

018

Pro

sp. c

ohor

t 44

His

tory

of

CS

, und

erw

ent

SH

G f

or v

arie

ty o

f gy

neco

logi

c in

dica

tions

Tria

ngul

ar a

nech

oic

stru

ctur

e at

pre

sum

ed

site

of

CS

sca

r

Pre

vale

nce

and

char

acte

ristic

s of

nic

he

on S

HG

100%

Wan

g, 2

00910

Cro

ss-s

ectio

nal

207*

H

isto

ry o

f C

S, e

xam

ined

on

TV

S f

or v

ario

us

gyne

colo

gica

l ind

icat

ions

, di

agno

sed

with

a C

S s

car

defe

ct

Hyp

oech

ogen

ic a

rea

with

in m

yom

etriu

m o

f LU

S a

t si

te o

f pr

evio

us

CS

inci

sion

Pre

vale

nce

of C

S s

car

defe

ct o

n TV

S7%

Upp

al, 2

01128

P

rosp

. coh

ort

71†

Ref

erre

d fo

r gy

neco

logi

cal u

ltras

ound

; 71

wom

en h

ad h

isto

ry o

f C

S

Flui

d-fil

led

defe

ct in

hy

ster

otom

y in

cisi

onFr

eque

ncy

and

appe

aran

ce o

f C

S s

car

defe

cts

on T

VS

in w

omen

w

ith h

isto

ry o

f C

S

40%

Dia

met

er o

f sc

ar d

efec

t (a

vera

ge in

long

itudi

nal

and

tran

sver

sal p

lane

s)

rang

ed f

rom

3 t

o 12

mm

w

ith m

ean

of 6

.5 m

m

Tabl

e 3

Con

tinue

d

Pop

ulat

ion

with

pos

tmen

stru

al s

pott

ing

and

hist

ory

of o

ne o

r m

ultip

le C

Ss

Cha

ng, 2

00927

Pro

sp. c

ohor

t 57

Pos

tmen

stru

al s

pott

ing

afte

r C

STr

iang

ular

ane

choi

c im

age

in a

nter

ior

low

er u

teru

s m

uscl

e, a

ttrib

utab

le t

o pr

ior

CS

del

iver

y

Pre

vale

nce

of C

S s

car

defe

ct o

n TV

S;

com

paris

on w

ith S

HG

co

ncer

ning

thi

ckne

ss o

f re

sidu

al m

yom

etriu

m a

nd

dept

h of

sca

r de

fect

(n

=22

)

88%

‡S

HG

sho

wed

sim

ilar

thic

knes

s of

res

idua

l m

yom

etriu

m a

nd la

rger

de

pth

of t

he C

S s

car

defe

ct in

com

paris

on w

ith

TVS

(p<

0.05

)

Bor

ges,

20

1013

Pro

sp. c

ohor

t 43

Pos

tmen

stru

al s

pott

ing

and

hist

ory

of C

S in

pr

eced

ing

2-25

yea

rs

On

HS

: cav

ity a

t sc

ar s

ite,

supe

rior

fibro

tic r

ing,

in

ferio

r fib

rotic

rin

g, b

lood

in

inva

gina

tion

site

and

ce

rvic

al c

anal

dia

met

er a

t he

ight

of

uppe

r fib

rosi

s

Pre

vale

nce

of is

thm

ocel

e w

ith H

S

88%

Pop

ulat

ion

with

nic

he d

emon

stra

ted

on T

VS

and

his

tory

of

one

or m

ultip

le C

Ss

Fabr

es, 2

0036

Ret

ro. c

ohor

t 92

His

tory

of

CS

and

pou

ch

at s

ite o

f C

S s

car

on T

VS

; H

S p

erfo

rmed

in 4

4% o

f pa

tient

s w

ith a

bnor

mal

ut

erin

e bl

eedi

ng

Filli

ng d

efec

t of

ute

rine

cavi

ty lo

cate

d in

rel

atio

n to

ant

erio

r is

thm

us

Des

crip

tion

of

sono

grap

hic

char

acte

ristic

s of

pou

ch

and

asse

ssm

ent

of

asso

ciat

ion

betw

een

TVS

an

d hy

ster

osco

py

In a

ll w

omen

def

ect

was

vi

sual

ized

as

tria

ngul

ar

anec

hoic

are

a w

ith b

ase

on p

oste

rior

wal

l of

cerv

ical

cha

nnel

and

ve

rtex

opp

osite

bas

e po

intin

g to

war

d an

terio

r w

all o

f is

thm

us; H

S

show

ed 1

00%

cor

rela

tion

with

TV

S in

det

ectio

n of

po

uch

Onl

y fir

st a

utho

r is

list

ed f

or e

ach

stud

y. *

4250

wom

en w

ith h

isto

ry o

f C

S e

xam

ined

. †To

tal n

=31

8 (7

1 w

ith p

revi

ous

CS

). ‡I

f ni

che

was

not

not

ed a

t fir

st v

isit,

TV

S w

as p

erfo

rmed

dur

ing

post

men

stru

al

spot

ting

(n=

18).

Sev

en w

omen

wer

e lo

st t

o fo

llow

-up

and

excl

uded

. HS

, hys

tero

scop

y; L

US

, low

er u

terin

e se

gmen

t; N

PV,

neg

ativ

e pr

edic

tive

valu

e; P

PV,

pos

itive

pre

dict

ive

valu

e; P

rosp

., pr

ospe

ctiv

e;

Ret

ro.,

retr

ospe

ctiv

e; s

ens.

, sen

sitiv

ity; S

HG

, con

tras

t-en

hanc

ed s

onoh

yste

rogr

aphy

; spe

c., s

peci

ficity

; TV

S=

tran

svag

inal

son

ogra

phy.


29


Tabl

e 3

Pre

vale

nce

of a

nic

he in

rela

tion

to d

iagn

osti

c m

etho

d in

a p

opul

atio

n of

wom

en w

ith

a hi

stor

y of

Ces

area

n se

ctio

n (C

S) a

nd g

ynec

olog

ical

sym

ptom

s (i

.e. s

ubje

ct to

sel

ecti

on b

ias)

Stu

dy

Des

ign

NP

op

ula

tio

nD

efin

itio

n o

f a

nic

he

Ou

tco

me

Nic

he

pre

vale

nce

o

n T

VS

(%

)

Nic

he

pre

vale

nce

o

n S

HG

(%

)

Nic

he

pre

vale

nce

o

n H

S (

%)

Res

ult

s

Pop

ulat

ion

unde

rgoi

ng g

ynec

olog

ical

ultr

asou

nd f

or a

var

iety

of

indi

catio

ns, w

ith h

isto

ry o

f on

e or

mul

tiple

CS

s

Ofil

i-Yeb

ovi,

2008

11

Pro

sp. c

ohor

t 32

4H

isto

ry o

f tr

ansv

erse

lo

wer

-seg

men

t C

S,

refe

rred

for

var

iety

of

gyne

colo

gica

l ind

icat

ions

Any

det

ecta

ble

thin

ning

of

myo

met

rium

at

site

of

CS

sca

r

Pre

vale

nce

of C

S s

car

defe

cts

and

desc

riptio

n of

m

orph

olog

ical

fea

ture

s on

TV

S

19%

Sca

r de

fect

sev

ere

(≥50

%

of d

epth

of

myo

met

rium

) in

10%

El-M

azny

, 20

1116

Cro

ss-s

ectio

nal

75H

isto

ry o

f C

S in

pr

eced

ing

1-5

year

s,

exam

ined

for

infe

rtili

ty,

men

stru

al d

isor

ders

or

recu

rren

t pr

egna

ncy

loss

Filli

ng d

efec

t in

CS

sca

r, de

fined

as

tria

ngul

ar,

anec

hoic

are

a at

pr

esum

ed s

ite o

f in

cisi

on

Acc

urac

y of

SH

G v

ersu

s go

ld s

tand

ard

HS

for

dete

ctio

n of

nic

he a

nd

thic

knes

s of

sca

r

27%

31%

SH

G c

ompa

rabl

e to

HS

as

show

n by

sen

s. (8

7%),

spec

. (10

0%),

PP

V

(100

%),

NP

V (9

5%) a

nd

over

all a

ccur

acy

(96%

) in

diag

nosi

s of

nic

he; s

car

thic

knes

s lo

wer

at

SH

G

than

at

HS

(P=

0.01

6)

Mon

teag

udo,

20

018

Pro

sp. c

ohor

t 44

His

tory

of

CS

, und

erw

ent

SH

G f

or v

arie

ty o

f gy

neco

logi

c in

dica

tions

Tria

ngul

ar a

nech

oic

stru

ctur

e at

pre

sum

ed

site

of

CS

sca

r

Pre

vale

nce

and

char

acte

ristic

s of

nic

he

on S

HG

100%

Wan

g, 2

00910

Cro

ss-s

ectio

nal

207*

H

isto

ry o

f C

S, e

xam

ined

on

TV

S f

or v

ario

us

gyne

colo

gica

l ind

icat

ions

, di

agno

sed

with

a C

S s

car

defe

ct

Hyp

oech

ogen

ic a

rea

with

in m

yom

etriu

m o

f LU

S a

t si

te o

f pr

evio

us

CS

inci

sion

Pre

vale

nce

of C

S s

car

defe

ct o

n TV

S7%

Upp

al, 2

01128

P

rosp

. coh

ort

71†

Ref

erre

d fo

r gy

neco

logi

cal u

ltras

ound

; 71

wom

en h

ad h

isto

ry o

f C

S

Flui

d-fil

led

defe

ct in

hy

ster

otom

y in

cisi

onFr

eque

ncy

and

appe

aran

ce o

f C

S s

car

defe

cts

on T

VS

in w

omen

w

ith h

isto

ry o

f C

S

40%

Dia

met

er o

f sc

ar d

efec

t (a

vera

ge in

long

itudi

nal

and

tran

sver

sal p

lane

s)

rang

ed f

rom

3 t

o 12

mm

w

ith m

ean

of 6

.5 m

m

Tabl

e 3

Con

tinue

d

Pop

ulat

ion

with

pos

tmen

stru

al s

pott

ing

and

hist

ory

of o

ne o

r m

ultip

le C

Ss

Cha

ng, 2

00927

Pro

sp. c

ohor

t 57

Pos

tmen

stru

al s

pott

ing

afte

r C

STr

iang

ular

ane

choi

c im

age

in a

nter

ior

low

er u

teru

s m

uscl

e, a

ttrib

utab

le t

o pr

ior

CS

del

iver

y

Pre

vale

nce

of C

S s

car

defe

ct o

n TV

S;

com

paris

on w

ith S

HG

co

ncer

ning

thi

ckne

ss o

f re

sidu

al m

yom

etriu

m a

nd

dept

h of

sca

r de

fect

(n

=22

)

88%

‡S

HG

sho

wed

sim

ilar

thic

knes

s of

res

idua

l m

yom

etriu

m a

nd la

rger

de

pth

of t

he C

S s

car

defe

ct in

com

paris

on w

ith

TVS

(p<

0.05

)

Bor

ges,

20

1013

Pro

sp. c

ohor

t 43

Pos

tmen

stru

al s

pott

ing

and

hist

ory

of C

S in

pr

eced

ing

2-25

yea

rs

On

HS

: cav

ity a

t sc

ar s

ite,

supe

rior

fibro

tic r

ing,

in

ferio

r fib

rotic

rin

g, b

lood

in

inva

gina

tion

site

and

ce

rvic

al c

anal

dia

met

er a

t he

ight

of

uppe

r fib

rosi

s

Pre

vale

nce

of is

thm

ocel

e w

ith H

S

88%

Pop

ulat

ion

with

nic

he d

emon

stra

ted

on T

VS

and

his

tory

of

one

or m

ultip

le C

Ss

Fabr

es, 2

0036

Ret

ro. c

ohor

t 92

His

tory

of

CS

and

pou

ch

at s

ite o

f C

S s

car

on T

VS

; H

S p

erfo

rmed

in 4

4% o

f pa

tient

s w

ith a

bnor

mal

ut

erin

e bl

eedi

ng

Filli

ng d

efec

t of

ute

rine

cavi

ty lo

cate

d in

rel

atio

n to

ant

erio

r is

thm

us

Des

crip

tion

of

sono

grap

hic

char

acte

ristic

s of

pou

ch

and

asse

ssm

ent

of

asso

ciat

ion

betw

een

TVS

an

d hy

ster

osco

py

In a

ll w

omen

def

ect

was

vi

sual

ized

as

tria

ngul

ar

anec

hoic

are

a w

ith b

ase

on p

oste

rior

wal

l of

cerv

ical

cha

nnel

and

ve

rtex

opp

osite

bas

e po

intin

g to

war

d an

terio

r w

all o

f is

thm

us; H

S

show

ed 1

00%

cor

rela

tion

with

TV

S in

det

ectio

n of

po

uch

Onl

y fir

st a

utho

r is

list

ed f

or e

ach

stud

y. *

4250

wom

en w

ith h

isto

ry o

f C

S e

xam

ined

. †To

tal n

=31

8 (7

1 w

ith p

revi

ous

CS

). ‡I

f ni

che

was

not

not

ed a

t fir

st v

isit,

TV

S w

as p

erfo

rmed

dur

ing

post

men

stru

al

spot

ting

(n=

18).

Sev

en w

omen

wer

e lo

st t

o fo

llow

-up

and

excl

uded

. HS

, hys

tero

scop

y; L

US

, low

er u

terin

e se

gmen

t; N

PV,

neg

ativ

e pr

edic

tive

valu

e; P

PV,

pos

itive

pre

dict

ive

valu

e; P

rosp

., pr

ospe

ctiv

e;

Ret

ro.,

retr

ospe

ctiv

e; s

ens.

, sen

sitiv

ity; S

HG

, con

tras

t-en

hanc

ed s

onoh

yste

rogr

aphy

; spe

c., s

peci

ficity

; TV

S=

tran

svag

inal

son

ogra

phy.


30

C h a p t e r 2

Niche sizeEight studies evaluated niche size, but the studies describing large niches used different

definitions for this.5,7,9,11,16,17,27,28 Vikhareva Osser et al.9 classified a niche as large or as a

total defect based on subjective evaluation in a random population of women with a history

of CS examined by TVS. At least one defect was classified as large in 14%, 23% and 45%

of the women with one, two and at least three CSs, respectively. At least one total defect

(with no remaining myometrium over the defect) was observed in 6%, 7% and 18% of

the women with one, two and at least three CSs, respectively. In another study by the

same authors, a niche was defined as large if the remaining myometrium measured ≤ 2.2 mm

in thickness using TVS and ≤ 2.5 mm using SHG in women with one previous CS.17 According

to the authors, these cut-off values were the measurements that best discriminated

between defects estimated subjectively as being large or not in women with a history of

one CS. Regnard et al.7 reported that two out of 19 niches (11%) had a depth of at least

80% of the anterior myometrium, which was demonstrated with SHG in a random

population of women with a history of CS. Ofili-Yebovi et al.11 demonstrated that, when

using TVS in a group of women with gynecological symptoms, half of them had a large

niche, i.e. one involving more than 50% of the myometrial thickness.

The above mentioned studies demonstrate that there is currently no uniform definition of

a large niche. The definitions used for a large niche were a niche penetrating to a depth of

at least 50% or 80% of the anterior myometrium, or the remaining myometrial thickness

≤ 2.2 mm when evaluated by TVS and ≤ 2.5 mm when evaluated by SHG. A total defect

was defined as no remaining myometrium over the defect.

Risk factorsRisk factors that are associated with the presence or size of a niche were evaluated in nine

studies (Table S1). Various risk factors were investigated, but none of the papers studied

exactly the same ones. In addition, some factors are known to be mutually related. For

example, several indications for CS (duration of labor, oxytocin augmentation) affect cervical

dilatation or the development of the lower uterine segment.22 For this reason, we classified

all risk factors into four main categories: factors related to closure technique, development

of the lower uterine segment or location of the incision, wound healing and miscellaneous

factors (Table 4). In addition, studies were classified according to their design, with studies

including only one previous CS and/or those using multivariate analysis presented first.

Three studies were performed in a population of women with a history of only one CS and

analyzed with the use of multivariate analysis, and will be discussed below.22,25,26

Closure techniqueTwo studies evaluated the relationship between closure technique and the presence of a

niche.25,26 A randomized controlled trial reported a lower frequency of a niche in women

treated by full thickness suturing (including the endometrial layer) in comparison with split

thickness suturing (excluding the endometrial layer)26, while a prospective cohort study

reported a reduced risk of niche development after double-layer myometrium closure or


31


single-layer myometrium closure with endometrial suture in comparison with single-layer

myometrium closure without endometrial suture.25 Another prospective cohort study

reported large niches more frequently in women with one-layer uterine closure (90.9%) in

comparison with two-layer closure (9.1%), but this was not a statistically significant

difference.22 A niche was classified as large in the latter study if the remaining myometrium

measured ≤ 2.2 mm in thickness using TVS and ≤ 2.5 mm in thickness using SHG.

Development of lower uterine segment or scar locationThree studies reported a relationship between the presence or size of a niche and the

factors potentially affecting the development of the lower uterine segment or scar location.

(Table 4)22,25,26 In one of these studies, the risk of a large niche increased if the station of

the presenting part of the fetus at CS was below the pelvic inlet, cervical dilatation

was ≥ 5 cm or duration of labor was ≥ 5 h.22 Another study, on the other hand, reported that

an increased risk for the presence of a niche was related to less cervical dilatation.26

Hayakawa et al.25 reported that an increased risk was associated with premature rupture

of membranes and increased gestational age at delivery, while Yazicioglu et al.26 found that

there was no relationship with gestational age. Emergency CS and the presence of labor

were reported not to be risk factors for the presence of a niche.25,26

Wound healingOne study reported a relationship between uterine retroflexion and a large niche, and

another reported a relationship between pre-eclampsia and the presence of a niche.22,25

We classified these risk factors as ones with a potential negative effect on wound healing.

Other factors that were classified in this category (infection or maternal body mass index)

were not related to the presence of a niche.25 In a study performed in women with a history

of one or multiple CSs, multivariate analysis demonstrated a relationship between the

presence of a niche and multiple CSs or uterine retroflexion.11

SymptomsThe identification of niche-related symptoms was evaluated in eight studies, using TVS, SHG

or hysteroscopy for niche assessment (Table S2). Two studies were performed in a random

population of women with a history of CS5,15; both studies fulfilled the STROBE criteria, except

for the correction for confounders in one study.15 Bij de Vaate et al.5 reported postmenstrual

spotting in 34% of women with a niche using SHG, which was significantly higher than in

women without a niche. Menada Valenzano et al.15 did not find an association between the

presence of a niche identified with SHG and abnormal uterine bleeding, defined as spotting

after the end of menstruation and/or non-cyclic bleeding not related to menstruation.

However, the same authors found that abnormal uterine bleeding was more frequent in

women with diverticula (anechoic round structures) and deformation of the cervical canal at

the scar site, identified on TVS. In addition, abnormal bleeding was more frequent in women

with a history of CS than in women with a previous vaginal birth in this study, indicating some

relationship between the presence of a CS scar and postmenstrual spotting.


32

C h a p t e r 2

Table 4 Classification of risk factors for presence or size of a Cesarean section (CS) scar niche

Vikh., 201022

Haya., 200625

Yazi., 200526

Ofil., 200811

Ceci, 201223

Glav., 201224

Arms., 20034

Wang, 200910

Mont., 20018

Study characteristics

Included patients (n) 108 137 70 324 60 149 32 207 44

Previous CSs (n) 1 1 1 ≥1 1 1 ≥1 ≥1 ≥1

Risk factors:

In multivariate analysis (n) 8 14 7 2 0 0 0 0 0

In univariate analysis (n) 20 0 0 8 1 1 2 2 1

For presence of niche/large niche Large Pres. Pres. Pres. Large Large Pres. Large Large

Reported potential risk factors for niche

Factors affecting closure technique

Suturing technique No Yes* Yes* NA Yes Yes NA NA NA

Years of surgical experience NA No* NA NA NA NA NA NA NA

Any closure factor related? No Yes* Yes* NA Yes Yes NA NA NA

Factors affecting development of LUS or lower location of incision

Advanced stage presenting part at CS Yes* NA NA NA NA NA NA NA NA

Scar at level of internal cervical os Yes NA NA No NA NA NA NA NA

Cervical dilatation Yes*§ NA Yes*¶ NA NA NA NA NA NA

Presence/duration of labor at CS Yes* NA No* NA NA NA Yes NA NA

Oxytocin during labor Yes NA NA NA NA NA NA NA NA

Premature rupture of membranes NA Yes* NA NA NA NA NA NA NA

Emergency CS No No* NA No NA NA NA NA NA

Gestational age at delivery Yes‡ Yes*† No* No NA NA NA NA NA

Any LUS factor related? Yes* Yes* Yes* No NA NA Yes NA NA

Factors with potential negative influence on wound healing

Multiple CSs NA NA NA Yes* NA NA Yes Yes No

Uterine retroflexion Yes* NA NA Yes* NA NA NA Yes NA

Diabetes ** NA NA NA NA NA NA NA NA

Steroids during pregnancy ** NA NA NA NA NA NA NA NA

Pre-eclampsia ** Yes* NA NA NA NA NA NA NA

Peri- or postpartum infection No No* NA NA NA NA NA NA NA

Intraoperative complications No NA NA NA NA NA NA NA NA

Maternal BMI No No* NA NA NA NA NA NA NA

Any healing factor related? Yes* Yes* NA Yes* NA NA Yes Yes No

Other

Maternal age Yes No* NA No NA NA NA NA NA

Multiple pregnancies NA Yes* NA No NA NA NA NA NA

Number of vaginal births No NA NA No NA NA NA NA NA

Placenta previa NA No* NA NA NA NA NA NA NA

Pfannenstiel or vertical incision NA No* NA NA NA NA NA NA NA

Intraoperative blood loss No No* NA NA NA NA NA NA NA

Platelets/hematocrit/hemoglobin No NA No* NA NA NA NA NA NA

Fetal weight NA NA No* NA NA NA NA NA NA

Regional or general anesthesia NA No* NA NA NA NA NA NA NA

Operating time NA NA No* NA NA NA NA NA NA

Only names of first authors are given, abbreviated to four letters. *Results obtained with use of multivariate analysis (parameters that were not risk factors were not included in this table). §More cervical dilatation. ¶Less cervical dilatation. ‡Decreased gestational age at delivery. †Increased gestational age at delivery. **Number of women too small for statistical calculations. BMI, body mass index; LUS, lower uterine segment; NA, not assessed; Pres, presence.


33


Six studies were performed in a population of women with gynecological symptoms (Table

S2), and a high prevalence of postmenstrual spotting in women with a niche compared

with women without a niche was reported in three studies.6,10,18 In one cross-sectional

study the prevalence of postmenstrual spotting in women with a niche examined by TVS

for various gynecological reasons was 64%.10 In a very small prospective cohort study all

women with a niche demonstrated by SHG had postmenstrual spotting.18 A retrospective

study of all TVS examinations conducted for a variety of gynecological reasons reported

abnormal bleeding in 83% and postmenstrual spotting in 76% of premenopausal women

with a niche.6

Three studies reported an association between the size of a niche and postmenstrual

spotting.5,10,28 In one study, performed in a random population of women with a history of

CS, the depth and shape of the niche were not significant factors, while a larger niche

volume was described in women with postmenstrual spotting.5 The other two studies,

performed in a population of women with gynecological symptoms, demonstrated that

niches were significantly wider in women with postmenstrual spotting, dysmenorrhea or

chronic pelvic pain, and that the prevalence of postmenstrual spotting or prolonged

menstrual bleeding was higher with a larger diameter of the niche.10,28 Other reported

symptoms in women with a niche were dysmenorrhea (53.1%), chronic pelvic pain (36.9%)

and dyspareunia (18.3%).10

Discussion

In a random population of women with a history of CS, the prevalence of a niche ranged

from 24% to 70% and 56% to 84% when assessed by TVS and SHG, respectively. Probable

risk factors are single-layer myometrium closure, multiple CSs and retroflexed uterus. The

predominant symptom related to a niche is postmenstrual spotting. The ideal study

reporting on symptoms would be performed in a random sample of women with a history

of CS in order to prevent selection bias, but also including a group of patients who had only

experienced vaginal birth in order to distinguish the effects of CS and niche. Only one study

performed in a random population described a positive relationship between a niche and

postmenstrual spotting.5 This association was not found by Menada Valenzano et al.15, who

did report a relationship between postmenstrual spotting and a previous CS. The

discrepancy in the findings of these two studies can be explained by variations in

methodology, such as definition of a niche, timing of the ultrasound scans and exclusion

of multiple CSs in the population of Menada Valenzano et al. In the majority of the studies

evaluating niches in women with gynecological symptoms, selection bias is likely to play

a role, which is underlined by the higher prevalence of postmenstrual spotting in these

women than in a random population of women with a history of CS.6,10,13,18,28 Several

hypotheses have been put forward to explain the etiology of abnormal uterine bleeding in

women with a niche, such as poor contractility of the uterine muscle around the niche,

which may result in retention of menstrual blood within it.18


34

C h a p t e r 2

Two studies report that closure technique during CS affects niche development. It seems

to be more appropriate to use double-layer or full thickness suturing, a finding that should

be confirmed in future studies.25,26 Although the results of the current review are

inconclusive, we hypothesize that potential factors affecting the development of the lower

uterine segment (such as duration of labor, dilatation, stage of the presenting part) may

influence development of a niche. It has been postulated that the characteristics of the

myometrium alter during labor and that, for example, a thinner myometrium may be less

well vascularized, which may lead to insufficient wound healing and niche development.29

In addition, a lower position of the CS incision, in particular in the cervical part of the uterus,

may be more prone to the development of a niche.9

The current review is the first systematic review to give an overview of the available

literature relating to the prevalence of a niche, potential risk factors and symptoms

associated with a niche. Given the inconsistency in methodology between the studies, we

were not able to perform meta-analyses. However, we ranked the included papers based

on criteria for quality assessment in order to improve the interpretation of the current

reported evidence.

The lack of consistency in methodology is based on three aspects. The principal issue was

the method of niche detection. Although TVS has been considered an accurate method

for detecting a niche, SHG may facilitate their detection and measurement, an idea that is

supported by the higher prevalence and identification of larger niches with SHG than with

TVS in two comparative studies.5,17 Application of saline or gel contrast enables

differentiation between niches that communicate with cervical wall defects and cervical

(mucous) cysts. In addition, small indentations or defects at the site of the scar can be

identified more precisely if contrast is used. Therefore, we propose SHG in non-pregnant

patients as the gold standard in future studies on niche prevalence.

The second major issue is the lack of agreement about the definition of a niche. First of

all, it is important to distinguish a niche from the CS scar itself. Naji et al.30 described a

standardized measurement technique and registration method for the evaluation of CS

scars using TVS in pregnant and non-pregnant women. However, there is no agreement

about how to define the margins of a niche, whether cervical diverticula should be included

or if there is a minimal size to the anechoic area for it to qualify as a niche. We propose

the following definition: any indentation representing myometrial discontinuity at the site

of the Cesarean scar that communicates with the uterine or cervical cavity as seen on SHG.

The problem with reporting on risk factors for a large niche is the lack of predefined

definitions for them. In one study, the cut-off value for a large niche was based on study

outcome, and therefore has a risk of data-driven definition.22 We propose the use of

predefined cut-off values for a large niche based on interquartile ranges or standard

deviations, or on the ratio of niche depth and total thickness of adjacent myometrium, e.g.

a ratio of more than 50%.11


35


Finally, there is significant heterogeneity in the patient populations reported, consisting of

women with a history of CS who were assessed for a variety of gynecological symptoms

or women with a history of CS (and vaginal birth), independent of their symptoms.

As the CS rate increases, the potential morbidity associated with CS scars is likely to

become increasingly important. If we are to understand the relevance of the presence of

a niche, it is essential that agreed criteria and definitions are used in future studies as well

as standardized outcomes. In addition, identification of potential risk factors provides insight

into etiology, but more importantly it would be useful for the prevention of future niche

development and related symptoms.

At present we do not know the importance of a niche in future pregnancies and it must

be questioned whether it is appropriate to report on the morphology of CS scars using

ultrasound in view of the fact that we do not know how to act on this information. It seems

increasingly likely that niches may be a cause of abnormal uterine bleeding, and we await

good interventional trials to see if correction in these circumstances is effective. The

possible impact of a niche on fertility is an important subject, but we have little information

on this topic to guide us.

In conclusion, niches are frequently identified after CS and are related to postmenstrual

spotting. A uniform definition of a niche and a method for assessment should be formulated

in order to enable future meta-analyses. We propose to use SHG and define a niche as any

indentation representing myometrial discontinuity at the site of the Cesarean scar that

communicates with the uterine or cervical cavity. More well-designed research on risk

factors is needed in order to obtain tools to prevent future niche development.

AcknowledgementsWe thank J.C.F. Ket for his assistance with the literature search.


36

C h a p t e r 2

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39


Appendix S1

Literature search

PubMed February 2013

Search Query Results

#4 #1 AND #2 AND #3 1370

#3 “Cesarean Section”[Mesh] OR cesarea*[tiab] OR caesarea*[tiab] OR “c section”[tiab] OR “c sections”[tiab] OR (abdominal[tiab] AND deliver*[tiab]) OR postcesarea*[tiab] OR postcaesaria*[tiab]

54595

#2 “Uterus”[Mesh] OR “Uterine Diseases”[Mesh] OR uterus[tiab] OR uterine[tiab] OR myometri*[tiab] OR endometri*[tiab] OR endomyometri*[tiab] OR myoendometri*[tiab]

266584

#1 “Cicatrix”[Mesh] OR cicatr*[tiab] OR scar[tiab] OR scars[tiab] OR scarring[tiab] OR isthmocele*[tiab] OR niche[tiab] OR niches[tiab] OR anechoic[tiab] OR pouch*[tiab] OR diverticul*[tiab]

119394

Embase February 2013

Search Query Results

#5 #1 AND #2 AND #3 AND [embase]/lim 1583

#4 #1 AND #2 AND #3 2057

#3 ‘cesarean section’/exp OR cesarea*:ab,ti OR caesarea*:ab,ti OR ‘c section’:ab,ti OR ‘c sections’:ab,ti OR (abdominal:ab,ti AND deliver*:ab,ti) OR postcesarea*:ab,ti OR postcaesarea*:ab,ti

66719

#2 ‘uterus’/exp OR ‘uterus disease’/exp OR uterus:ab,ti OR uterine:ab,ti OR myometri*:ab,ti OR endometri*:ab,ti OR endomyometri*:ab,ti OR myoendometri*:ab,ti

485605

#1 ‘wound dehiscence’/exp OR ‘scar formation’/exp OR ‘scar’/exp OR cicatr*:ab,ti OR scar:ab,ti OR scars:ab,ti OR scarring:ab,ti OR isthmocele*:ab,ti OR niche:ab,ti OR niches:ab,ti OR anechoic:ab,ti OR pouch*:ab,ti OR diverticul*:ab,ti

151943


40

C h a p t e r 2

Appendix S2

STROBE checklist

Description of items Vikhareva Osser and Valentin (2010)

Bij de Vaate et al. (2011)

Glavind et al. (2012)

Hayakawa et al. (2006)

Valenzanoet al. (2006)

Yazicioglu (2006)

Vikhareva Osser et al. (2010)

Vihareva Osser et al. (2009)

Ofili-Yebovi et al. (2008)

El-Mazny et al. (2011)

Wang et al. (2009)

1a Study design is clear in title or abstract 1 1 1 1 1 1 0 0 0 1 1

b Abstract provides an informative and balanced summary 1 1 1 1 1 1 1 1 1 1 1

2 Explain the scientific background and rationale for the investigation being reported 1 1 1 1 1 1 1 1 1 1 1

3 State specific objectives, including any prespecified hypotheses 1 1 1 1 1 1 1 1 1 1 1

4 Present key elements of study design early in the paper 1 1 1 1 1 1 0 0 0 1 1

5 Describe the setting, locations, and relevant dates, includingperiods of recruitment, exposure, follow-up, and data collection

1 1 1 1 1 1 0 0 0 0 0

6a Give the eligibility criteria and the sources and methods of selection of participants; describe methods of follow-up

1 1 1 1 1 1 1 1 1 1 0

b For matched studies, give matching criteria and number of exposed and unexposed NA NA NA NA 1 NA NA NA NA NA NA

7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers; give diagnostic criteria, if applicable

1 1 1 1 1 0 1 1 1 1 1

8 For each variable of interest, give data sources and details of methods of assessment 1 1 1 1 1 1 1 1 1 1 1

9 Describe any efforts to address potential sources of bias 1 1 0 0 1 1 1 1 0 0 0

10 Explain how the study size was arrived at 1 1 1 1 1 1 1 1 0 0 0

11 Explain how quantitative variables were handled in the analyses; if applicable, describe which groupings were chosen and why

0 0 0 0 0 0 0 0 1 0 0

12a Describe all statistical methods 1 1 1 1 1 1 1 1 1 1 1

b Describe any methods used to examine subgroups and interactions NA NA NA NA 0 NA NA NA NA NA NA

c Explain how missing data were addressed 0 0 0 0 0 0 0 0 0 0 0

d Explain how loss to follow-up was addressed NA NA NA NA NA 0 NA NA NA NA NA

e Describe any sensitivity analyses NA NA NA NA NA NA NA NA NA NA NA

13a Report numbers of individuals at each stage of study 1 1 1 1 1 1 1 1 1 1 1

b Give reasons for non-participation at each stage 1 1 1 1 1 1 1 1 1 1 1

c Consider use of a flow diagram 0 1 1 0 0 0 0 0 0 0 0

14a Give characteristics of study participants and information on exposures and potential confounders

1 1 1 1 1 1 1 1 1 1 0

b Indicate number of participants with missing data for each variable of interest NA 1 NA NA NA 1 NA NA 1 NA NA

c Summarize follow-up time NA NA NA NA NA NA NA NA NA NA NA

15 Report numbers of outcome events or summary measures over time 1 1 1 1 1 1 1 1 1 1 1

16a Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision 1 1 0 1 0 1 0 0 1 0 1

b Report category boundaries when continuous variables were categorized 1 NA NA NA NA NA 0 0 NA NA NA

c If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period

0 0 0 0 0 0 0 0 0 0 0

17 Report other analyses done NA NA NA NA NA NA NA NA NA NA NA

18 Summarize key results with reference to study objectives 1 1 1 1 0 0 1 1 1 1 1

19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. 1 0 1 1 0 0 1 1 0 0 1

20 Give a cautious overall interpretation of results 1 1 1 1 1 1 1 1 1 1 1

21 Discuss the generalisability of the study results 0 0 0 0 0 0 0 0 0 0 0

22 Give funding sources 1 0 1 0 0 0 1 1 0 0 0

Summary22/27(81.5%)

21/27 (77.8%)

20/26 (76.9%)

19/26 (73.1%)

18/28(64.3%)

18/28 (64.3%)

17/27(63.0%)

17/27(63.0%)

16/27(59.3%)

15/26(57.7%)

15/26(57.7%)


41


Description of items Vikhareva Osser and Valentin (2010)

Bij de Vaate et al. (2011)

Glavind et al. (2012)

Hayakawa et al. (2006)

Valenzanoet al. (2006)

Yazicioglu (2006)

Vikhareva Osser et al. (2010)

Vihareva Osser et al. (2009)

Ofili-Yebovi et al. (2008)

El-Mazny et al. (2011)

Wang et al. (2009)

1a Study design is clear in title or abstract 1 1 1 1 1 1 0 0 0 1 1

b Abstract provides an informative and balanced summary 1 1 1 1 1 1 1 1 1 1 1

2 Explain the scientific background and rationale for the investigation being reported 1 1 1 1 1 1 1 1 1 1 1

3 State specific objectives, including any prespecified hypotheses 1 1 1 1 1 1 1 1 1 1 1

4 Present key elements of study design early in the paper 1 1 1 1 1 1 0 0 0 1 1

5 Describe the setting, locations, and relevant dates, includingperiods of recruitment, exposure, follow-up, and data collection

1 1 1 1 1 1 0 0 0 0 0

6a Give the eligibility criteria and the sources and methods of selection of participants; describe methods of follow-up

1 1 1 1 1 1 1 1 1 1 0

b For matched studies, give matching criteria and number of exposed and unexposed NA NA NA NA 1 NA NA NA NA NA NA

7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers; give diagnostic criteria, if applicable

1 1 1 1 1 0 1 1 1 1 1

8 For each variable of interest, give data sources and details of methods of assessment 1 1 1 1 1 1 1 1 1 1 1

9 Describe any efforts to address potential sources of bias 1 1 0 0 1 1 1 1 0 0 0

10 Explain how the study size was arrived at 1 1 1 1 1 1 1 1 0 0 0

11 Explain how quantitative variables were handled in the analyses; if applicable, describe which groupings were chosen and why

0 0 0 0 0 0 0 0 1 0 0

12a Describe all statistical methods 1 1 1 1 1 1 1 1 1 1 1

b Describe any methods used to examine subgroups and interactions NA NA NA NA 0 NA NA NA NA NA NA

c Explain how missing data were addressed 0 0 0 0 0 0 0 0 0 0 0

d Explain how loss to follow-up was addressed NA NA NA NA NA 0 NA NA NA NA NA

e Describe any sensitivity analyses NA NA NA NA NA NA NA NA NA NA NA

13a Report numbers of individuals at each stage of study 1 1 1 1 1 1 1 1 1 1 1

b Give reasons for non-participation at each stage 1 1 1 1 1 1 1 1 1 1 1

c Consider use of a flow diagram 0 1 1 0 0 0 0 0 0 0 0

14a Give characteristics of study participants and information on exposures and potential confounders

1 1 1 1 1 1 1 1 1 1 0

b Indicate number of participants with missing data for each variable of interest NA 1 NA NA NA 1 NA NA 1 NA NA

c Summarize follow-up time NA NA NA NA NA NA NA NA NA NA NA

15 Report numbers of outcome events or summary measures over time 1 1 1 1 1 1 1 1 1 1 1

16a Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision 1 1 0 1 0 1 0 0 1 0 1

b Report category boundaries when continuous variables were categorized 1 NA NA NA NA NA 0 0 NA NA NA

c If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period

0 0 0 0 0 0 0 0 0 0 0

17 Report other analyses done NA NA NA NA NA NA NA NA NA NA NA

18 Summarize key results with reference to study objectives 1 1 1 1 0 0 1 1 1 1 1

19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. 1 0 1 1 0 0 1 1 0 0 1

20 Give a cautious overall interpretation of results 1 1 1 1 1 1 1 1 1 1 1

21 Discuss the generalisability of the study results 0 0 0 0 0 0 0 0 0 0 0

22 Give funding sources 1 0 1 0 0 0 1 1 0 0 0

Summary22/27(81.5%)

21/27 (77.8%)

20/26 (76.9%)

19/26 (73.1%)

18/28(64.3%)

18/28 (64.3%)

17/27(63.0%)

17/27(63.0%)

16/27(59.3%)

15/26(57.7%)

15/26(57.7%)


42

C h a p t e r 2

Table S1 Risk factors for the presence of a niche and factors associated with niche size

Leading author Design N Population Outcome Definition of niche and method of evaluation Results

Random sample of women with a history of CS,

reporting about factors associated with the presence of a niche:

Yazicioglu et al. 200526

Randomized controlled trial

70 Nullipar pregnant patients with an indication for CS, with or without labour.

The effect of suturing technique (full thickness including the endometrial layer versus split thickness excluding the endometrial layer) on the incidence of cesarean scar defect.

Definition: Any deviation from the full apposition of the cranial and caudal edges of the uterine incision causing a ballooning out towards the anterior abdominal wall.Method: TVS

The frequency of incomplete healing was significantly lower in the group treated by full thickness suturing (OR 0.2 [95% CI 0.06-0.99]; p=0.048). Patients with incomplete healing had less cervical dilatation prior to surgery (OR 0.5 [95% CI 0.3-0.8]; p=0.007).

Hayakawa et al. 200625

Prospective cohort study

137 Women who underwent first CS between 26 and 41 weeks of gestation with a transverse lower uterine segment incision, with or without labour.

Association between wedge defect one month after CS and method for myometrium closure as well as other perioperative parameters.

Definition: Concavity at the presumed site of incision with a depth of more than 5 mm. Method: TVS

Factors associated with wedge defect were myometrium closure technique (double-layer: OR 0.3 [95% CI 0.09-0.9]; p=0.04), single-layer with decidual suture: OR 0.08 [95% CI 0.01-0.5]; p=0.007), gestational week (OR 1.4 [95% CI 1.1-1.8]; p=0.02), multiple pregnancies (OR 8.9 [95% CI 2.0-40.6]; p=0.005), premature rupture of membranes (OR 8.7 [95% CI 1.3-59.7]; p=0.03) and pre-eclampsia (OR 8.7 [95% CI 1.7-44.5]; p=0.009).

Armstrong et al. 20034


32 with previous CS (n=70)

Volunteers between ages 18 and 40 with a history of one or multiple vaginal (n=38) or cesarean deliveries (n=32) within the preceding 5 years.

Association between cesarean scar defects and the obstetric history.

Definition: Fluid within the scar and incontinuity with the endocervical canal. Method: TVS

Prolonged labour prior to cesarean delivery (p=0.01) and multiple CSs (p<0.04) were associated with the presence of cesarean scar defects.

reporting about factors associated with niche size:

Vikhareva Osser and Valentin 201022 (subgroup of Vikhareva Osser et al. 20099)


108 Women with a history of one CS in the preceding 6-9 months.

Factors increasing the risk of large cesarean scar defects in women with a history of only one CS.

Definition: Any indentation in the scar, however small. Method: TVS and SHG.

Increased cervical dilatation at CS (0 cm, 1-4 cm, 5-7 cm, ≥8 cm; OR 4.4 [95% CI 0.7-28.5], 26.5 [4.3-161.8], 32.4 [6.1-171.0]; p<0.001) and station of the presenting part at CS below pelvic inlet (OR 14.1 [95% CI 4.6-43.1]; p<0.001) were independent variables associated with a large niche. Retroflexed uterus (OR 2.9 [95% CI 1.0-8.3]; p=0.047) and duration of active labour (0, 1-4, 5-9, ≥10 hours; OR 2.0 [95% CI 0.2-23.8], 13.0 [2.2-76.6], 33.1 [6.6-166.9]; p<0.001) were also associated with a large niche.

Ceci et al. 201223


60 Singleton primiparae who were not in labour and underwent their first CS.

The outcome of the cesarean scar, comparing 2 types of single-layer sutures (locked continuous vs. interrupted sutures).

Definition: Bell-shaped pouch area. Method: TVS and hysteroscopy.

The prevalence of a uterine wall defect was 85.7%, and the area under the pouch was larger in women with continuous sutures as compared to interrupted sutures (p=0.03). Hysteroscopy confirmed the presence of the pouches, but different hysteroscopic outcomes were observed.

Glavind et al. 201224

Retrospective cohort study

149 Women who underwent their first CS in singleton pregnancy at least 6 months ago and who were not in labour.

A difference in residual myometrial thickness and size of the cesarean scar defect between single- and double-layer uterotomy closure.

Definition: Any indented wedge-shaped area stretching beyond the suggested anterior lining of the endometrium. Method: TVS

The median residual myometrial thickness was 5.8 mm in double-layer vs. 4.6 mm in single-layer closures (p=0.04). The scar defect length decreased from 6.8 mm in single-layer to 5.6 mm in double-layer closures (p=0.01). Height and width were similar in both groups.

Selected population consisting of women with gynaecological symptoms,


Ofili-Yebovi et al. 200811


324 Women with a history of one or multiple transverse lower-segment CSs, referred for a variety of gynaecological indications.

The identification of factors associated with the presence of cesarean scar defects.

Definition: Detectable myometrial thinning at the scar site. Method: TVS

A history of multiple CSs (OR 1.9 [95% CI 1.3-2.9]; p=0.001), uterine retroflexion (OR 2.4 [95% CI 1.3-4.8]; p=0.01) and the inability to visualize all cesarean scars in women with a history of multiple CSs (OR 0.31 [95% CI 0.13-0.75]; p=0.01) were associated with the presence of cesarean scar defects.


Wang et al. 200910

Cross-sectional study

207 Women with a history of one or multiple CSs, examined with TVS for various gynaecological indications, diagnosed with a cesarean scar defect.

Association between the size of cesarean scar defects, uterine position and the number of CSs.

Definition: Hypoechogenic area within the myometrium of the lower uterine segment, at the site of a previous cesarean incision. Method: TVS

The mean width and depth of the scar defect were larger in women who had undergone multiple CSs (p=0.001 and p=0.002) and the mean width was larger in women with a retroflexed uterus (p<0.001).

Monteagudo et al. 20018


44 Women with a history of one or multiple CSs, who underwent SHG for a variety of gynaecologic indications.

Association between the number of CSs and the size of the niche and thickness of the residual myometrium.

Definition: Triangular anechoic structure at the site of a previous cesarean scar. Method: SHG

There was no association between the number of CSs and the depth of the niche or the thickness of the residual myometrium.

CS=cesarean section; TVS=transvaginal sonography; SHG=sonohysterography


43


Table S1 Risk factors for the presence of a niche and factors associated with niche size

Leading author Design N Population Outcome Definition of niche and method of evaluation Results

Random sample of women with a history of CS,


Yazicioglu et al. 200526

Randomized controlled trial

70 Nullipar pregnant patients with an indication for CS, with or without labour.

The effect of suturing technique (full thickness including the endometrial layer versus split thickness excluding the endometrial layer) on the incidence of cesarean scar defect.

Definition: Any deviation from the full apposition of the cranial and caudal edges of the uterine incision causing a ballooning out towards the anterior abdominal wall.Method: TVS

The frequency of incomplete healing was significantly lower in the group treated by full thickness suturing (OR 0.2 [95% CI 0.06-0.99]; p=0.048). Patients with incomplete healing had less cervical dilatation prior to surgery (OR 0.5 [95% CI 0.3-0.8]; p=0.007).

Hayakawa et al. 200625


137 Women who underwent first CS between 26 and 41 weeks of gestation with a transverse lower uterine segment incision, with or without labour.

Association between wedge defect one month after CS and method for myometrium closure as well as other perioperative parameters.

Definition: Concavity at the presumed site of incision with a depth of more than 5 mm. Method: TVS

Factors associated with wedge defect were myometrium closure technique (double-layer: OR 0.3 [95% CI 0.09-0.9]; p=0.04), single-layer with decidual suture: OR 0.08 [95% CI 0.01-0.5]; p=0.007), gestational week (OR 1.4 [95% CI 1.1-1.8]; p=0.02), multiple pregnancies (OR 8.9 [95% CI 2.0-40.6]; p=0.005), premature rupture of membranes (OR 8.7 [95% CI 1.3-59.7]; p=0.03) and pre-eclampsia (OR 8.7 [95% CI 1.7-44.5]; p=0.009).

Armstrong et al. 20034



Volunteers between ages 18 and 40 with a history of one or multiple vaginal (n=38) or cesarean deliveries (n=32) within the preceding 5 years.

Association between cesarean scar defects and the obstetric history.

Definition: Fluid within the scar and incontinuity with the endocervical canal. Method: TVS

Prolonged labour prior to cesarean delivery (p=0.01) and multiple CSs (p<0.04) were associated with the presence of cesarean scar defects.


Vikhareva Osser and Valentin 201022 (subgroup of Vikhareva Osser et al. 20099)


108 Women with a history of one CS in the preceding 6-9 months.

Factors increasing the risk of large cesarean scar defects in women with a history of only one CS.

Definition: Any indentation in the scar, however small. Method: TVS and SHG.

Increased cervical dilatation at CS (0 cm, 1-4 cm, 5-7 cm, ≥8 cm; OR 4.4 [95% CI 0.7-28.5], 26.5 [4.3-161.8], 32.4 [6.1-171.0]; p<0.001) and station of the presenting part at CS below pelvic inlet (OR 14.1 [95% CI 4.6-43.1]; p<0.001) were independent variables associated with a large niche. Retroflexed uterus (OR 2.9 [95% CI 1.0-8.3]; p=0.047) and duration of active labour (0, 1-4, 5-9, ≥10 hours; OR 2.0 [95% CI 0.2-23.8], 13.0 [2.2-76.6], 33.1 [6.6-166.9]; p<0.001) were also associated with a large niche.

Ceci et al. 201223


60 Singleton primiparae who were not in labour and underwent their first CS.

The outcome of the cesarean scar, comparing 2 types of single-layer sutures (locked continuous vs. interrupted sutures).

Definition: Bell-shaped pouch area. Method: TVS and hysteroscopy.

The prevalence of a uterine wall defect was 85.7%, and the area under the pouch was larger in women with continuous sutures as compared to interrupted sutures (p=0.03). Hysteroscopy confirmed the presence of the pouches, but different hysteroscopic outcomes were observed.

Glavind et al. 201224


149 Women who underwent their first CS in singleton pregnancy at least 6 months ago and who were not in labour.

A difference in residual myometrial thickness and size of the cesarean scar defect between single- and double-layer uterotomy closure.

Definition: Any indented wedge-shaped area stretching beyond the suggested anterior lining of the endometrium. Method: TVS

The median residual myometrial thickness was 5.8 mm in double-layer vs. 4.6 mm in single-layer closures (p=0.04). The scar defect length decreased from 6.8 mm in single-layer to 5.6 mm in double-layer closures (p=0.01). Height and width were similar in both groups.

Selected population consisting of women with gynaecological symptoms,


Ofili-Yebovi et al. 200811


324 Women with a history of one or multiple transverse lower-segment CSs, referred for a variety of gynaecological indications.

The identification of factors associated with the presence of cesarean scar defects.

Definition: Detectable myometrial thinning at the scar site. Method: TVS

A history of multiple CSs (OR 1.9 [95% CI 1.3-2.9]; p=0.001), uterine retroflexion (OR 2.4 [95% CI 1.3-4.8]; p=0.01) and the inability to visualize all cesarean scars in women with a history of multiple CSs (OR 0.31 [95% CI 0.13-0.75]; p=0.01) were associated with the presence of cesarean scar defects.


Wang et al. 200910


207 Women with a history of one or multiple CSs, examined with TVS for various gynaecological indications, diagnosed with a cesarean scar defect.

Association between the size of cesarean scar defects, uterine position and the number of CSs.

Definition: Hypoechogenic area within the myometrium of the lower uterine segment, at the site of a previous cesarean incision. Method: TVS

The mean width and depth of the scar defect were larger in women who had undergone multiple CSs (p=0.001 and p=0.002) and the mean width was larger in women with a retroflexed uterus (p<0.001).



44 Women with a history of one or multiple CSs, who underwent SHG for a variety of gynaecologic indications.

Association between the number of CSs and the size of the niche and thickness of the residual myometrium.

Definition: Triangular anechoic structure at the site of a previous cesarean scar. Method: SHG

There was no association between the number of CSs and the depth of the niche or the thickness of the residual myometrium.

CS=cesarean section; TVS=transvaginal sonography; SHG=sonohysterography


44

C h a p t e r 2

Table S2 Symptoms associated with the presence of a niche

Leading author

Design N Population Outcome Definition of niche and method of evaluation

Specification of bleeding disorder and method of evaluation

Results

No selection bias, random sample of women with a history of CS:

Bij de Vaate et al. 20115


225 Consecutive inclusion of women 6-12 months after a CS.

Relationship between niche and abnormal uterine bleeding.

Definition: Anechoic area at the site of the cesarean scar with a depth of at least 1 mm.Method: SHG

Postmenstrual spotting: More than 2 days of brownish discharge at the end of the menstruation with a total length of menstruation of more than 7 days, or intermenstrual bleeding which starts within 5 days after the end the end of the menstruation. Method: Questionnaire and PBAC.

Postmenstrual spotting was reported by 34% of women with a niche and 15% without a niche (p=0.002). Larger niche volume was seen in women with postmenstrual spotting than without postmenstrual spotting (p=0.02,) and no relation was found between niche shape and postmenstrual spotting.

Valenzano et al. 200615

Case-control study


Random selection of women who gave birth for the first time between 1995 and 2004: vaginal birth (n=101) or CS (n=116).

Association between morphological changes of the lower uterine segment after CS and the frequency of abnormal uterine bleeding.

Definition: Triangular, anechoic area at the presumed site of incision.Method: TVS, and only niches with SHG

Abnormal uterine bleeding: Spotting bleeding after the end of the menstruation and/or non-cyclic bleeding not related to the menstruation. Method: Questions were asked.

Abnormal bleeding was more frequent in the CS group as compared with the vaginal birth group (p=0.041). No association was found between abnormal bleeding and the presence of a niche (p=0,818), but an association was found with diverticula (p=0.012) and deformation of the cervical canal (p=0.031), which was more significant in women who had a CS 5-10 years ago.

Selected population consisting of women with gynaecological symptoms:

Uppal et al. 201128



Women referred for gynaecological ultrasound. 71 women had a history of CS.

Association between cesarean scar defects and abnormal vaginal bleeding.

Definition: Fluid filled defect in the hysterotomy incision.Method: TVS

Abnormal bleeding pattern: periods longer than 7 days and/or spotting after the period. Method: Questionnaire and records of the women were reviewed.

The presence of a cesarean scar defect was significantly associated abnormal bleeding (OR 1.96 [95% CI 1.16-3.32]; p<0.05). The larger the defect, the higher was the incidence of abnormal vaginal bleeding.

Thurmond et al. 199918


310 Women referred for abnormal uterine bleeding, who were evaluated with SHG, independent of their obstetric history.

Description of a cause of abnormal vaginal bleeding related to a history of CS.

Definition: A gap in the anterior lower uterine segment myometrium at the expected site of the scar from prior cesarean deliveries.Method: SHG

Postmenstrual spotting: 2 to 12 days of postmenstrual discharge of dark red or brown material. Method: Not specified.

9 women with a history of CS

demonstrated a niche and all these women had a history of 2 to 12 days of postmenstrual spotting.

Wang et al. 200910


207 Women with a history of CS, examined with TVS for various gynaecological indications, diagnosed with a cesarean scar defect.

The prevalence of various clinical symptoms in patients with cesarean scar defects and the assessment of the association between the size of the cesarean scar defect and symptoms.

Definition: Hypoechogenic area within the myometrium of the lower uterine segment, at the site of a previous cesarean incision.Method: TVS

Bleeding disorder not defined. Method: Medical histories were reviewed. Questionnaires and missing data were obtained by direct phone contact.

Prolonged postmenstrual spotting was the most common symptom (64%), followed by dysmenorrhea (53%), chronic pelvic pain (40%) and dyspareunia (18%). The mean defect width was significantly larger in women with postmenstrual spotting (p<0.001), dysmenorrhea (p=0.001) and chronic pelvic pain (p<0.001). No association between depth or thickness of the residual myometrium and symptoms was found.

Fabres et al. 20036


92 Premenopausal women with a history of CS and a pouch at the site of the cesarean scar demonstrated with TVS, who were assessed for other gynaecological reasons.

Association between the presence of the pouch and bleeding disturbances.

Definition: A filling defect of the uterine cavity located in relation to the anterior isthmus.Method: TVS

Bleeding disorder and method not defined.

83% of the women with a pouch had abnormal uterine bleeding. Among these women, 76% had postmenstrual spotting, 16% midcycle metrorrhagia and 6% both symptoms.



44 Women with a history of CS, who underwent SHG for a variety of gynaecologic indications.

The prevalence of abnormal uterine bleeding in women with a niche.

Definition: Triangular anechoic structure at the presumed site of a CS scar.Method: SHG


75% of women with a niche had abnormal uterine bleeding, 36% had fibroids and 18% had endometrial polyps.

Borges et al. 201013


43 Women with postmenstrual spotting and a history of CS in the preceding 2-25 years.

Assessment of the hysteroscopy findings in women with a history of CS and postmenstrual spotting, stressing the diagnosis of isthmocele.

Definition not specified.Method: Hysteroscopy


The hysteroscopic diagnosis of isthmocele was conclusive in 38 patients (88.4%). The average time of postmenstrual spotting was 6 years and the mean duration of each episode was 6 days.

CS=cesarean section; TVS=transvaginal sonography; SHG=sonohysterography; PBAC=pictorial bloodloss assessment chart


45


Table S2 Symptoms associated with the presence of a niche

Leading author

Design N Population Outcome Definition of niche and method of evaluation

Specification of bleeding disorder and method of evaluation

Results

No selection bias, random sample of women with a history of CS:

Bij de Vaate et al. 20115


225 Consecutive inclusion of women 6-12 months after a CS.

Relationship between niche and abnormal uterine bleeding.

Definition: Anechoic area at the site of the cesarean scar with a depth of at least 1 mm.Method: SHG

Postmenstrual spotting: More than 2 days of brownish discharge at the end of the menstruation with a total length of menstruation of more than 7 days, or intermenstrual bleeding which starts within 5 days after the end the end of the menstruation. Method: Questionnaire and PBAC.

Postmenstrual spotting was reported by 34% of women with a niche and 15% without a niche (p=0.002). Larger niche volume was seen in women with postmenstrual spotting than without postmenstrual spotting (p=0.02,) and no relation was found between niche shape and postmenstrual spotting.

Valenzano et al. 200615

Case-control study


Random selection of women who gave birth for the first time between 1995 and 2004: vaginal birth (n=101) or CS (n=116).

Association between morphological changes of the lower uterine segment after CS and the frequency of abnormal uterine bleeding.

Definition: Triangular, anechoic area at the presumed site of incision.Method: TVS, and only niches with SHG

Abnormal uterine bleeding: Spotting bleeding after the end of the menstruation and/or non-cyclic bleeding not related to the menstruation. Method: Questions were asked.

Abnormal bleeding was more frequent in the CS group as compared with the vaginal birth group (p=0.041). No association was found between abnormal bleeding and the presence of a niche (p=0,818), but an association was found with diverticula (p=0.012) and deformation of the cervical canal (p=0.031), which was more significant in women who had a CS 5-10 years ago.

Selected population consisting of women with gynaecological symptoms:

Uppal et al. 201128



Women referred for gynaecological ultrasound. 71 women had a history of CS.

Association between cesarean scar defects and abnormal vaginal bleeding.

Definition: Fluid filled defect in the hysterotomy incision.Method: TVS

Abnormal bleeding pattern: periods longer than 7 days and/or spotting after the period. Method: Questionnaire and records of the women were reviewed.

The presence of a cesarean scar defect was significantly associated abnormal bleeding (OR 1.96 [95% CI 1.16-3.32]; p<0.05). The larger the defect, the higher was the incidence of abnormal vaginal bleeding.

Thurmond et al. 199918


310 Women referred for abnormal uterine bleeding, who were evaluated with SHG, independent of their obstetric history.

Description of a cause of abnormal vaginal bleeding related to a history of CS.

Definition: A gap in the anterior lower uterine segment myometrium at the expected site of the scar from prior cesarean deliveries.Method: SHG

Postmenstrual spotting: 2 to 12 days of postmenstrual discharge of dark red or brown material. Method: Not specified.

9 women with a history of CS

demonstrated a niche and all these women had a history of 2 to 12 days of postmenstrual spotting.

Wang et al. 200910


207 Women with a history of CS, examined with TVS for various gynaecological indications, diagnosed with a cesarean scar defect.

The prevalence of various clinical symptoms in patients with cesarean scar defects and the assessment of the association between the size of the cesarean scar defect and symptoms.

Definition: Hypoechogenic area within the myometrium of the lower uterine segment, at the site of a previous cesarean incision.Method: TVS

Bleeding disorder not defined. Method: Medical histories were reviewed. Questionnaires and missing data were obtained by direct phone contact.

Prolonged postmenstrual spotting was the most common symptom (64%), followed by dysmenorrhea (53%), chronic pelvic pain (40%) and dyspareunia (18%). The mean defect width was significantly larger in women with postmenstrual spotting (p<0.001), dysmenorrhea (p=0.001) and chronic pelvic pain (p<0.001). No association between depth or thickness of the residual myometrium and symptoms was found.

Fabres et al. 20036


92 Premenopausal women with a history of CS and a pouch at the site of the cesarean scar demonstrated with TVS, who were assessed for other gynaecological reasons.

Association between the presence of the pouch and bleeding disturbances.

Definition: A filling defect of the uterine cavity located in relation to the anterior isthmus.Method: TVS


83% of the women with a pouch had abnormal uterine bleeding. Among these women, 76% had postmenstrual spotting, 16% midcycle metrorrhagia and 6% both symptoms.



44 Women with a history of CS, who underwent SHG for a variety of gynaecologic indications.

The prevalence of abnormal uterine bleeding in women with a niche.

Definition: Triangular anechoic structure at the presumed site of a CS scar.Method: SHG


75% of women with a niche had abnormal uterine bleeding, 36% had fibroids and 18% had endometrial polyps.

Borges et al. 201013


43 Women with postmenstrual spotting and a history of CS in the preceding 2-25 years.

Assessment of the hysteroscopy findings in women with a history of CS and postmenstrual spotting, stressing the diagnosis of isthmocele.

Definition not specified.Method: Hysteroscopy


The hysteroscopic diagnosis of isthmocele was conclusive in 38 patients (88.4%). The average time of postmenstrual spotting was 6 years and the mean duration of each episode was 6 days.

CS=cesarean section; TVS=transvaginal sonography; SHG=sonohysterography; PBAC=pictorial bloodloss assessment chart


201725 proefschrift Lucet vd Voet compleet.indd 18 … 2.pdfstudies5,7,8,15-18,22 and hysteroscopy...

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