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Is Early Treatment with a Cervical Pessary an Option in Patients with a History of Surgical Conisation and a Short Cervix?

Authors:
  • Clara Angela Foundation, Witten and Berlin, Germany

Abstract

Objective: Patients with a history of one or more conizations have an increased risk of spontaneous preterm birth (SPTB). The aim of this study was to investigate the outcome of pregnancies in patients with a history of conization and early treatment with a cervical pessary. Methods: In this pilot observational study we included 21 patients and evaluated the obstetric history, the interval between pessary placement and delivery, gestational age at delivery, the neonatal outcome and the number of days of maternal and neonatal admission. Results: Among the study group of 21 patients, 20 patients had a singleton and one had a dichorionic/diamniotic twin pregnancy. At insertion, the mean gestational age was 17 + 2 (10 + 5-24 + 0) weeks and the mean cervical length was 19 (4-36) mm. Six patients presented with funneling at insertion with a mean funneling width of 19.7 (10-38) mm and funneling length of 19.9 (10-37) mm. Five patients had already lost at least one child due to early spontaneous preterm birth and another five had at least one previous abortion, who have now delivered beyond 34 weeks. The mean gestational age at delivery was 38 (31 + 1-41 + 0) gestational weeks and the mean interval between insertion and delivery was 145 (87-182) days. Conclusion: Our findings suggest a beneficial effect of an early pessary placement for patients at high-risk for preterm birth due to conization.
Abstract
!
Objective: Patients with a history of one or more
conizations have an increased risk of spontaneous
preterm birth (SPTB). The aim of this study was to
investigate the outcome of pregnancies in pa-
tients with a history of conization and early treat-
ment with a cervical pessary.
Methods: In this pilot observational study we in-
cluded 21 patients and evaluated the obstetric
history, the interval between pessary placement
and delivery, gestational age at delivery, the neo-
natal outcome and the number of days of mater-
nal and neonatal admission.
Results: Among the study group of 21 patients, 20
patients had a singleton and one had a dichorion-
ic/diamniotic twin pregnancy. At insertion, the
mean gestational age was 17 + 2 (10 + 524 + 0)
weeks and the mean cervical length was 19 (4
36) mm. Six patients presented with funneling at
insertion with a mean funneling width of 19.7
(1038) mm and funneling length of 19.9 (10
37) mm. Five patients had already lost at least
one child due to early spontaneous preterm birth
and another five had at least one previous abor-
tion, who have now delivered beyond 34 weeks.
The mean gestational age at delivery was 38
(31 + 141 + 0) gestational weeks and the mean
interval between insertion and delivery was 145
(87182) days.
Conclusion: Our findings suggest a beneficial ef-
fect of an early pessary placement for patients at
high-risk for preterm birth due to conization.
Zusammenfassung
!
Ziel: Schwangere Patientinnen nach Konisation
haben ein erhöhtes Risiko für eine Frühgeburt.
Das Ziel der vorliegenden Studie war die prospek-
tive Beobachtung einer Kohorte von Schwanger-
schaften nach einer oder mehreren Konisationen
und früher Behandlung mit einem zervikalen Pes-
sar.
Methoden: In dieser Pilotstudie wurden ins-
gesamt 21 Patientinnen rekrutiert. Es wurden
die geburtshilfliche Anamnese, die Zervixlänge
und die Zervixstruktur (Funneling) mithilfe trans-
vaginaler Sonografie, die Prolongation der
Schwangerschaft, das Gestationsalter bei der Ent-
bindung, sowie das neonatale Outcome und die
Tage des Aufenthalts von Müttern und Kindern
erfasst.
Ergebnisse: Das Kollektiv umfasste 21 Patientin-
nen, 20 Patientinnen hatten eine Einlings- und
1 Patientin hatte eine dichoriale/diamniale Zwil-
lingsschwangerschaft. Beim Einlegen des Pessars
betrug das mittlere Gestationsalter 17 + 2 (10 +
524 + 0) Schwangerschaftswochen (SSW) und
die mittlere Zervixlänge 19 (436) mm. Sechs Pa-
tientinnen zeigten eine Trichterbildung bereits
beim Einlegen des Pessars mit einer mittleren
Breite von 19,7 (1038) mm und einer mittleren
Länge von 19,9 (1037) mm. Fünf Patientinnen
hatten bereits ein Kind aufgrund von Frühgeburt-
lichkeit verloren und 5 weitere Patientinnen hat-
ten mindestens eine Fehlgeburt in der Anamnese,
welche in der aktuellen Schwangerschaft nach
der 34. SSW entbunden haben. Das mittlere Ges-
tationsalter bei Entbindung war 38 (31 + 1
41 + 0) SSW und die mittlere Zeit zwischen Ein-
legen des Pessars und Entbindung betrug 145
(87182) Tage.
Schlussfolgerung: Unsere Ergebnisse zeigten ei-
nen nützlichen Effekt der frühzeitigen Behand-
lung mit Pessar für Risikoschwangerschaften nach
Konisation.
Is Early Treatment with a Cervical Pessary
an Option in Patients with a History
of Surgical Conisation and a Short Cervix?
Ist die frühe Behandlung mit einem zervikalen Pessar eine Option
für Patientinnen nach Konisation und Zervixverkürzung?
Authors I. Kyvernitakis, R. Khatib, N. Stricker, B. Arabin
Affiliation Department of Gynecology and Obstetrics, Philipps-University of Marburg, Marburg
in cooperation with the Clara Angela Foundation, Witten
Key words
l
"conisation
l
"pessary
l
"cerclage
l
"cervical shortening
l
"preterm birth
Schlüsselwörter
l
"Konisation
l
"Pessar
l
"Cerclage
l
"Zervixverkürzung
l
"Frühgeburt
received 7. 9. 2014
revised 20. 10. 2014
accepted 26. 10. 2014
Bibliography
DOI http://dx.doi.org/
10.1055/s-0034-1383271
Geburtsh Frauenheilk 2014; 74:
10031008 © Georg Thieme
Verlag KG Stuttgart · New York ·
ISSN 00165751
Correspondence
Dr. Ioannis Kyvernitakis, MD
Philipps-University of Marburg
Department of Gynecology
and Obstetrics
Baldingerstraße 1
35033 Marburg
kyvernit@med.uni-marburg.de
1003
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Introduction
!
A history with one or more surgical conizations increases the risk
of spontaneous preterm birth (SPTB). Ortoft et al. investigated the
outcome in patients who had undergone a surgical conization.
They reported a 2.8-fold increased perinatal death rate, an almost
5-fold risk for SPTB after a single and a 10-fold risk for SPTB after
two cone biopsies in subsequent pregnancies [1]. The proportion
of muscular and collagen content of the cervix varies [24].
Smooth muscle tissue decreases from the region of the internal
(29%) towards the external os (6%) [2]. Consequently, a cold knife
cone biopsy removes the collagen-rich part of the cervix. There-
fore, the etiology of cervical shortening after cone biopsies is dif-
ferent compared to onlyprecocious cervical ripening. Clinical
findings and more recent proteomic studies have suggested that
the cervical mucus plug plays an important role in the mainte-
nance of pregnancy by protecting the intrauterine cavity from as-
cending infection [5, 6]. Since the remaining endocervical canal
containing cervical mucus is short, this may represent an addi-
tional risk for ascending infections. Finally, a progressive opening
of the internal os may lead to cervical dilatation and preterm
rupture of membranes in patients with or without a history of
conization, but dilatation may occur earlier in patients with a his-
tory of conization.
Abdominal cerclage has been proposed as an option in patients
where the cervix had been completely removed either by trache-
lectomy or by repetitive conizations [7]. Up to now, both a pro-
phylactic and an emergency cerclage have failed to reduce the
rate of SPTB in patients with a history of conization [811]. In pa-
tients with cervical shortening but enough cervical tissue to be
surrounded by a pessary, abdominal cerclage might be avoided
[13].
Recently, Goya et al. have shown that the application of an Arabin
cervical pessary, when applied in mid trimester after detecting a
short cervical length (CL) in a screening population can signifi-
cantly reduce the rate of poor composite neonatal outcome in
singleton pregnancies by prolonging pregnancy [14]. Encouraged
by previous studies [15] in different risk settings as summarized
recently [16], we evaluated the course of pregnancies with cervi-
cal shortening after at least one conization and early treatment
with a cervical pessary.
The primary aim of this descriptive study was to investigate the
mean interval between pessary placement and delivery in this
high-risk group of patients with short cervix and former coniza-
tion. Apart from this, we regularly followed the cervical length
and report on the mode of delivery.
Methods
!
Patient recruitment
Patients with a history of late abortion, early SPTB and/or a con-
ization with significant tissue reduction are usually referred to
our preterm birth clinic in the first and second trimester or at
least when first symptoms of threatening SPTB are present. All
pregnant women transferred to our unit due to at least one cold
knife conization between 2010 and 2013 were examined by both
speculum investigation and transvaginal sonography (TVS),
whereby the CL was detected as described by Iams et al. [17]. At
least 3 measurements of the CL were performed during a 3-min-
ute interval and the shortest value was obtained for the calcu-
lations. All patients had undergone combined first trimester
screening with sonographic markers according to the Fetal Med-
icine Foundation (FMF) to exclude fetuses at risk for chromosom-
al abnormalities [18]. This patient group received no additional
progesteron, in order to avoid further treatment bias.
Clinical assessment and pessary placement
Twenty-one patients were included in the study when the cervi-
co-isthmic complex in the first trimester, correlating to the inner
CL in the second trimester, was below the 10th centile according
to Salomon [19] and when there was enough remaining cervical
tissue so that a pessary with an inner diameter of 32 mm could be
fixed around the cervix without the risk of displacement. The pa-
tients were informed about the up-to-date knowledge of success
rates of a cerclage and the pioneer treatment of pessary treat-
ment for this indication, which was approved by our ethics com-
mittee. Both a speculum examination and TVS were used for in-
dication and a control examination directly after the first inser-
tion of the pessary (Arabin pessary, approved in Europe for the
indication to prevent SPTB: CE0482, MED/CERT ISO 9003/EN
46003). When patients presented in the first trimester, a pessary
of 32 mm (upper diameter), 17 mm (height) and 65 or 70 mm
(lower diameter, primi-or multiparous women) was chosen, dur-
ing the second trimester only the height was changed to 21 mm
[16]. It has been demonstrated that even the pessary of 25 mm
height was not limiting sexual intercourse in the pessary arm as
opposed to controls in patients of the trial by Goya et al. [14] (per-
sonal communication). Patients with a pessary of only 17 mm
have even less complaints of discharge or mechanical distur-
bance.
Patients were followed in our unit whereby the CL was examined
as described previously [20]. Only two specialists were involved
in the indication, application, surveillance and follow-up.
Statistical analysis
After delivery, we evaluated the mean interval between pessary
placement and delivery, the neonatal outcome as well as the total
days of hospital admission. Statistical analysis was performed by
Excel (Office Mac 2011). l
"Table 1 demonstrates the history, re-
sult of TVS before therapy, gestational age at insertion, the course
and outcome of the pregnancy.
Details of ethics approval
The ethics committee of the University Hospital of Marburg gave
permission to perform the study as part of a clinical approach,
which had already been accepted as a clinical management in pa-
tients at risk for preterm delivery.
Results
!
Baseline characteristics of the patient population
Our study population included 20 singleton pregnancies (case 1
20) and 1 dichorionic-diamniotic (DCDA) twin pregnancy (case
21). Data of our study group are shown in l
"Table 1.
All patients had a history of at least one conization before the cur-
rent pregnancy. Median interval between the first conization and
the index pregnancy was 4.5 (19) years. Indication for the con-
ization was a repetitive Papanicolaou smear test of III D or worse,
following the current German guideline of 2014 [21]. Histopath-
ologic examination had shown that 4/21 patients had a mild cer-
vical intraepithelial neoplasia (CIN I), another 4/21 a moderate
CIN (CIN II) and 10/21 severe dysplasia (CIN III). The remaining
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Table 1 Descriptive data of the study group.
Patient Gravida/
Para
History of de-
liveries 37
weeks after
conisation
History of abortion
and/or SPTB after
conisation (gesta-
tional weeks)
Gestational age at
pessary placement
(gestational
weeks + days)
Cervical length
(mm) at pessary
placement
Cervical length
(mm)
2nd trimester
(with pessary)
Cervical length
(mm)
3rd trimester
(with pessary)
Gestational age
at delivery
(gestational
weeks+ days)
Interval
(days)
Mode of
delivery
Birth weight
(g)
1 G5P1 0 3×1216
1×20
22 + 3 4 15 17 37 + 3 105 C 2 910
2 G2 P1 0 1 × 21 12 + 0 36 25 26 40 + 1 197 V 3 540
3 G2 P0 0 1 × 15 23 + 6 16 18 19 40 + 0 113 C 4 080
4 G1 P0 0 0 17 + 2 19 23 25 36 + 3 134 C 2 720
5 G2 P1 0 0 23 + 6 24 25 28 40 + 3 116 V 3 450
6 G1 P0 0 0 10 + 5 18 26 5 41 + 0 212 V 3 130
7 G3 P2 1 0 20 + 3 6 27 10 32 + 6 87 V 2 300
8 G3 P2 0 0 13 + 6 10 14,5 15 31 + 1 121 V 1 980
9 G2 P0 0 1 × 14 14 + 1 28 29 25 39 + 1 175 C 3 770
10 G3 P2 0 0 22 + 3 16 16 18 36 + 2 97 C 2 810
11 G2 P1 0 1× 19 21 + 0 21 21,5 24 39 + 4 130 V 3 570
12 G4 P3 1 2× 1622 23 + 4 14 15 17 40 + 1 116 V 4 280
13 G1 P0 0 0 18 + 2 7 23 15 40 + 2 154 V 3 850
14 G1 P0 0 0 11 + 0 28 25 23 37 + 4 186 C 2 700
15 G2 P1 0 0 18 + 0 14 23 17,2 35 + 2 121 V 2 360
16 G3 P2 0 0 14 + 5 20 25 28 39 + 3 173 V 3 035
17 G1 P0 0 0 12 + 2 18 28 26 40 + 2 196 V 3 200
18 G1 P0 0 0 12 + 6 24 27 24 35 + 6 161 V 2 820
19 G1 P0 0 0 13 + 2 25 26 28 40 + 5 192 V 3 100
20 G5 P1 1 3× 1216 24 + 0 21 21 26 39 + 2 107 V 3 000
21 G7 P4 1 2× 1622 11 + 5 31 20 18 34 + 2 158 C 2 206; 2290
Mean
total
17 + 2
(10 + 524 + 0)
19
(436)
22,5
(1529)
20,7
(528)
38
(31 + 141 + 0)
145
(87212)
3 050
(1 9804 280)
G = Gravida, P = Para, SPTB = Spontaneous preterm birth, C = Cesarean delivery, V = Vaginal delivery
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3/21 patients had a chronic cervicitis. To better scrutinize the in-
vasive nature of a cone biopsy, the dimensions of the removed
tissue were retrospectively evaluated. The dimensions ranged be-
tween 1.3 × 1.3 × 0.2 cm and 4 × 2.5 × 0.3 cm. In two patients a
second conization was indicated because of infested dysplastic
cells on the edge of the cone.
In the index pregnancy, the mean gestational age at TVS indicat-
ing a pessary insertion was 17 + 2 (10 + 524 + 0) gestational
weeks and the mean cervical length (CL) was 19 (436) mm. Six
patients presented with funneling at insertion with a mean pro-
portion of funneling width of 19.7 (1038) mm and funneling
length of 19.9 (1037) mm.
Five patients (24%) had already lost at least one child due to early
SPTB before viability after conization, whereby 3/21 patients
(14%) among them the patient with DCDA twins had already
lost 2 children between 16 and 22 weeks due to cervical insuffi-
ciency. All of these patients delivered beyond 34 weeks, the pa-
tient with the twin pregnancy underwent a primary Caesarean
delivery due to preeclampsia at 34 +2 gestational weeks. Five pa-
tients (24%) had a history with previous abortion. Seven/21 pa-
tients (33%) were primiparous. l
"Fig. 1 demonstrates the mean
course of CL during the course of pregnancy as calculated from
l
"Table 1.
Outcome of the patient population
The mean gestational age at delivery was 38 + 0 (31 + 141 + 0)
weeks and the mean interval between insertion and delivery
was 145 (87182) days. The mean duration of admission during
pregnancy was 11 (028) days. Indications for admission were
intermediate premature contractions (n = 5), preeclampsia
(n = 2), suspicion of intrauterine growth retardation (n = 1) or in-
termediate feelings of insecurity at early gestational age com-
bined with a long distance from home in patients with previous
immature birth (n = 5).
Indications for a Caesarean delivery included pathologic fetal
heart rate (FHR) tracing (case 1), prolonged labour (case 3, 4,
14), severe condylomata accuminata (case 9), breech presenta-
tion (case 10), and preeclampsia in a twin gestation (case 21).
Immediate neonatal outcome of all newborns was uneventful,
20/21 newborns were discharged with their mothers 25days
after delivery, only one infant (case 3) was admitted to our neo-
natal unit for 10 days due to prematurity, but had no symptoms
of respiratory distress syndrome, brain injury, neonatal sepsis or
necrotizing enterocolitis.
Discussion
!
The results of the present study indicate that treatment with a
cervical pessary leads to a clinically important elongation of the
cervival length, which resulted in a mean interval between pes-
sary insertion and delivery of 145 (87182) days. As such, we re-
port a mean gestational age at delivery of 38 + 0 (31 + 141 + 0)
weeks. The mean duration of admission during pregnancy was
11 (028) days.
In 2012, Greco et al. have shown that prediction of SPTB is feasi-
ble in the first trimester [22]. Between 11 and 13 weeks, the au-
thors measured the linear distance of the glandular area of the
endocervical canal and the cervico-isthmic complex in singleton
pregnancies. There are still discrepant views how to measure the
CL in both the first and the second trimester. Most investigators
still use the standard techniquedescribed by Iams et al. [17],
which correlates to the cervico-isthmic complex in the first tri-
mester. Vayssiere et al. used this technique in twin gestations
[23], according to the authorʼs opinion the inter-operator var-
iance is less compared to the technique of measuring only the
part bordered by the endocervical mucosa (personal communi-
cation). In any case, normal values of both techniques differ since
the absolute values are higher when using the standard tech-
nique. Therefore, the criteria of cervical measurements have to
be strictly defined when starting or comparing multicentre trials.
Castanon et al. explored the association of conization and SP TB in
a cohort of patients undergoing colposcopy in 12 National Health
Service hospitals in Great Britain [26]. The authors reported a
SPTB-rate of 9.0 % after a simple punch biopsy during colposcopy
or a rate of 9.4% after a superficial conization respectively (RR
1.41, p = 0.03). In comparison, the average SPTB rate in England
in the past decade was 6.7%. Interestingly, the proportion of SPTB
varied widely by hospital from 6.215.6% according to the size of
the average cone. These data are consistent with the study of
Poon et al. who reported a significant association between large
loop excision procedure (LEEP) and the risk of SPTB, even after
adjustment of maternal risk factors [27]. In our population, gyne-
cologists only performed the cold knife conization. In contrast to
the cold-knife conization, LEEP helps to conserve the cervical
stroma volume. Patient selection for cold-knife conization favors
those at highest risk for invasive cancer including cervical cytol-
ogy suspicious for invasive cancer, patients older than 35 years
with CIN III or carcinoma in situ, large high-grade lesions, and bi-
opsies showing endocervical adenocarcinoma [28].
The Arabincervical pessary was already demonstrated in Ger-
man book chapters 30 years ago [16], but the first pilot study us-
ing TVS of the CL as a reference in singleton and twin pregnancies
was published just 10 years ago [29]. In 2012, Goya et al. per-
formed the first randomised trial using TVS and recruiting the
planned sample size of 385 singleton pregnancies with a CL
25 mm at 1822 gestational weeks for randomisation. Thereby
the rate of SPTB before 34 weeks of gestation was reduced from
Cervical length
40
35
30
25
20
15
10
5
0
Pessary
placement
2nd
trimester
3rd
trimester
Highest CL
Lowest CL
Mean CL
Fig. 1 Mean values of the cervical length (CL) at pessary placement, and
during subsequent measurements in the second and third trimester
(n = 21). The mean CL changed from 19 (436) mm at pessary placement
to 22.5 (1529) mm and 20.7 (528) mm in the second and third trimester
respectively. The elongation of the CL resulted into a clinically important
interval between placement and delivery.
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27 to 6%, as well as the rate of SPTB before 32 and 28 weeks. The
rate of adverse neonatal outcome was significantly better in the
pessary compared to the control group (RR: 0.2; 95% CI 0.1 to
0.4) [14]. However, patients with a history of cone biopsy had
been excluded from this study. Notably, cervical pessaries have
not proven to be efficient in the preventing setting, when the CL
is longer than 25 mm [30]. We have previously shown that ab-
dominal cerclage was even successful in preventing early SPTB
in a twin pregnancy with complete removal of cervical tissue
[12]. However, abdominal cerclage is invasive and requires exper-
tise of the surgeon [24]. As such, in patients with a history of a
conization both a prophylactic and a therapeuticcerclage in pa-
tients with cervical shortening have failed to effectively prevent
SPTB [811, 25].
In 2013, the so-called Pro-Twin trial recruited 813 women with
multiple pregnancies in the Netherlands [31]. Patients were ran-
domised to either pessary or expectant management between 16
and 20 weeks. Although there was no difference in the primary
outcome of all twin pregnancies, composite poor neonatal out-
come (perinatal death or severe morbidity), was significantly
lower in a prespecified subgroup of women who had a CL below
25th percentile (< 38 mm) at 1620 gestational weeks and a pes-
sary treatment. A study performed by the FMF did not yet find a
positive effect of the pessary in twin gestations although the data
are not yet published. In both studies, the compliance and possi-
bly the results could have been improved by teaching, patient in-
formation or audit procedures [27]. Another study, which has not
yet been published, has found a significant reduction in SPTB be-
fore 34 gestational weeks in twin pregnancies randomized in the
second trimester when the CL was < 25 mm (Carreras, personal
communication). In the only patient with a twin pregnancy in
our pilot study, the pessary was placed as early as possible, e.g.
at 11 + 5 gestational weeks. This patient had already 2 abortions
before the conization and had lost 2 children between 16 and 22
gestational weeks due to cervical insufficiency after the coniza-
tion. The CL at pessary placement at 11 + 5 weeks was 31 mm.
This t win pregnancy was prolonged up to 34 + 2 gestational
weeks, when a Caesarean delivery was indicated due to pre-
eclampsia.
Interestingly, the mean CL increased during the course of preg-
nancy in some patients after pessary insertion from the first to
the second trimester (l
"Table 1,Fig. 1). Clinical examinations
have suggested that the longer the pessary stays in place, the
greater is the chance that the cervix develops some degree of
thickening or edema at least in some patients. More objectively,
this has now been confirmed using Magnetic Resonance Tomog-
raphy (MRI) by Cannie et al. demonstrating that the pessary
changes the inclination of the cervical canal relative to the uterus
and that this persisted as long as the pessary remained in situ
[32]. In addition, the authors demonstrated an elongation and
even disappearance of funneling in some patients. This might ex-
plain that direct pressure on the membranes and the cervical in-
tegrity at the level of internal cervical os is reduced, which might
be more crucial in patients with a history of a conization.
Strengths and limitations
Our pilot study has limitations. Since data were only recruited
within one center, the number of patients is too small to make fi-
nal conclusions about the effects of early pessary treatment in
patients with a history of conization and a short CL early in preg-
nancy. All patients were referrals, which might have created a se-
lection bias and in addition, TVS was not performed in all patients
with a history of conization at a pre-defined gestational age
what should be done in future trials. Furthermore, the descrip-
tive nature of the study did not allow us to compare our results
with a control group. Therefore, it is not possible to make conclu-
sions, how the pregnancy outcome would be, without any inter-
vention.
The strength of our pilot study is that vaginal cerclage has not
been shown to be effective, the value of progestagens not (yet)
been evaluated in this pre-specified subgroup and that the cervi-
cal pessary might be an alternative as suggested by the fair out-
come even in patients who had a history of previous late miscar-
riages. Nevertheless, therapeutic negligence, e.g. not to offer any
therapeutic option in patients who have already lost a child or
are obviously at high risk to loose a child may be difficult for ob-
stetricians in charge.
Conclusion
Our observational findings from this pilot study suggest that the
cervical pessary leads to a clinically important long interval be-
tween pessary insertion and delivery, does not do harm and as
already suggested for twin pregnancies with a short cervix might
be a cost-effective and non-invasive option for patients with a
history of conization [33, 34]. The results in those few patients
who had already lost children due to cervical insufficiency and
now have been treated before 12 gestational weeks let us specu-
late that some effects of early cervical pessary treatment might
be beneficial. Further prospective randomized trials, recruiting
patients before 20 weeks of gestation are neccessary.
As mentioned previously, the best answers to clinical problems
will come from large international collaboration[16].
Acknowledgements
!
The authors thank the study participants for their contribution to
clinical research.
Contribution to Authorship
!
IK and BA conceived the study, participated in its design and co-
ordination, helped to draft the manuscript and made substantial
contributions to analysis and interpretation of the data. RK and
NS participated in the design of the study and made substantial
contributions to acquisition of data. All authors read and ap-
proved the final manuscript.
Funding: Nil
Conflict of Interest
!
The senior author Prof. Birgit Arabin has a direct ownership inter-
est in the company that manufactures pessaries including those
used in the study. The company is privately held and the profit is
used to support the Clara Angela Foundation for Research and
Development. The other authors have no conflict of interests.
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... [2] Conization removes the collagen-rich component and shortens the length of the cervical canal, leading to earlier dilatation and prostaglandin release. [3] The presence of residual cancer may also affect the integrity of cervical tissue and function. [4] Management options for pregnancy in a woman with a short cervix after conization and inadequate oncological margins is highlighted in our case. ...
... An Arabin pessary is known to reduce the risk of PTB in asymptomatic women with a short cervix. [3,11,13,14] Previous studies have also demonstrated the effectiveness of the combination of pessary and vaginal progesterone, compared with progesterone alone for preventing PTB. [11,12] Placement of the pessary does not disrupt cervical tissue, and it likely works by changing the angle of the cervix posteriorly. ...
... [11,12] Placement of the pessary does not disrupt cervical tissue, and it likely works by changing the angle of the cervix posteriorly. [3] A commonly reported side-effect of the pessary is increased vaginal discharge due to fluid accumulating behind it, which is then released through perforations. [13] This can be alarming in the context of an underlying cancer, which also presents with increased and malodorous vaginal discharge, especially if there has been progression. ...
Article
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Surgical conization of the cervix for cervical cancer increases the risk of preterm birth in subsequent pregnancies. The ideal intervention to prevent preterm births in women with cervical insufficiency resulting from conization is not known. When histological margins of the cone biopsy are suspected to have residual malignancy, surveillance and oncological management during a concurrent pregnancy can be challenging. This case outlines the management of a pregnancy complicated by a short cervix secondary to conization for adenocarcinoma of cervix, with margins suspected to be not clear of disease. The patient had progressive shortening of the cervix despite vaginal progesterone, but maintained a cervical length of 16 mm following Arabin pessary insertion. She delivered a healthy neonate at 34 + 3 weeks of gestation (105 days following pessary insertion). The cervical pessary in combination with vaginal progesterone may be safe and effective in preventing preterm birth in a pregnancy with possible residual cervical cancer and a short cervix.
... Три дослідження (n=1420) було включено в огляд ефективності використання песарію [14,17,24]. Песарій був застосований у всіх трьох дослідженнях. ...
Article
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Premature birth is a significant problem in modern medicine. The main aspects of its solution are the prediction and prevention of premature birth. Nowadays, among a large number of biophysical and biochemical markers of preterm birth, ultrasonic cevicometry is the most popular one. It is known that «short cervix syndrome» is not the equivalent of cervical insufficiency. The known strategies of preventive combinations are used in case of an increased risk of preterm birth. Therefore, the issue of developing a differentiated approach to the combined or separate use of progesterone, pessary, or cerclage has not been answered yet. It should be added that in most practical recommendations based on the principles of evidence-based medicine, there are no differences according to the possible pathogenesis of preterm birth. A therapeutic strategy should be set based on the possible use or misuse of any preventive combination, taking into account maternal and fetal contraindications. The combined testing on ultrasound cervicometry and biochemical markers could ameliorate the identification of patients at risk of preterm birth. The fetal fibronectin is known to be the best among all biochemical markers of preterm birth. However, the prognostic value of this test, as well as the phosphorylated transport protein insulin-like growth factor, when used separately, is limited. In pregnant women with a length of the cervix between 1.5 cm and 3 cm, it is recommended to use the analysis for placental alpha-microglobulin-1. The administration of corticosteroids should only be performed when the risk of preterm delivery is confirmed by decreased cervical length and a positive test for placental alpha-microglobulin-1 (there is a high risk of preterm delivery within 7 days). The cerclage is indicated in patients with cervical insufficiency before 16 weeks of gestation. In the presence of a «short cervix» and the lack of anamnestic data, the strategy should be individualized. The efficacy of cerclage or pessary application has not been proven. It is necessary to start with vaginal progesterone administration. In the process of the patient observation (cervicometry in dynamics) will allow you to find out an effective method: cerclage or pessary and vaginal progesterone. In the case of progredient cervical effacement in the second trimester, it is advisable to perform an urgent cerclage. In the case of incompetent cervical stitch, the additional application of a pessary is possible. In women with multiple pregnancies, there is no evidence of elective cerclage or pessary efficacy. However, it is possible to use heroic cerclage, pessary in combination with vaginal progesterone or vaginal progesterone monotherapy
... A further risk derives from patients with previous surgical conization because of removal of the most collagen-rich part of the cervix. In this high-risk group, the risk of sPTB is five times higher than in the reference population, while the risk for perinatal mortality is almost three times higher [10,11]. ...
Article
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Background: Patients with cervical shortening obtained by transvaginal ultrasound and/or previous preterm delivery are at increased risk for preterm birth in the current pregnancy. The aim of the present cohort study was to compare the rate of preterm birth and early neonatal parameters in patients at risk and screening patients who received either a cerclage or a combined treatment of cerclage and cervical pessary. Methods: A retrospective cohort study was conducted from March 2005 to March 2017 including all patients in our department which received a McDonald cerclage or a combined treatment of McDonald cerclage and an Arabin pessary. A total of 81 women with singleton pregnancies were considered the final sample of this cohort study, of whom 34 patients received a cerclage and 47 patients received a cerclage combined with a pessary. Patients “at risk” with a history of preterm birth at <37 weeks of gestation, late-term abortion, conization, or cervical cerclage in a previous pregnancy because of a cervical shortening <10th percentile and women with no inherent historic risk factors but a current cervical length <3rd percentile (screening group) were analyzed separately. We defined delivery <34 weeks of gestation as the primary outcome. Secondary outcomes were preterm birth (PTB) <28, <32, and <37 weeks of gestation, admission to the neonatal intensive care unit (NICU), neonatal admission time, birthweight, and prolongation of the gestation. Results: There were no differences between the two study groups with regard to baseline characteristics. Delivery <34 weeks of gestation occurred in 32.4 and 27.7% of patients treated with cerclage versus combined treatment respectively (p = .48). Similarly, there was no difference in the rate of preterm birth at <28, <32, or <37 weeks of gestation. The mean neonatal admission time at the neonatal intensive care unit was shorter in the combined treatment group versus in the cerclage group (p = .02). There was a trend for higher birthweight (2368 g ± 962 vs. 2650 g ± 1063) in favor of the combined treatment arm (p = .077). Conclusion: The combined treatment of cerclage with an Arabin pessary seems to be a considerable alternative in the prevention of spontaneous PTB (sPTB), especially for patients with cervical length <3rd percentile, and in particular for patients with amnion prolapse in terms of birthweight and neonatal admission time.
... After a conisation, Ortoft et al. [50] reported a 2.8-fold increased perinatal death rate, an almost 5-fold risk for sPTB after a single and a 10-fold risk after two cone biopsies in subsequent pregnancies [81]. While a cerclage could not reduce sPTB rates in these high-risk pregnancies [82,83], a prolongation of pregnancy was observed after pessary application during the first trimester within a pilot observational study [84]. However, neither for patients with a history of sPTB nor for patients with a conisation RCTs have been published. ...
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ABSTR AC T Preterm birth is one of the major global health problems and part of the Millennium Development goals because of the associated high number of perinatal or neonatal mortality and long-term risks of neurodevelopmental and metabolic diseases. Transvaginal sonography has meanwhile been established as a screening tool for spontaneous preterm birth despite its relatively low sensitivity when considering only the cervical length. Vaginal progesterone has been shown to reduce prematurity rates below 34 weeks in a screening population of singleton pregnancies. Up to now, no positive long-term effect could be demonstrated after 2 years. It seems to have no benefit to prolong pregnancies after a period of pre-term contractions and in risk patients without cervical shortening. Meta-analyses still demonstrate conflicting results dependent on quality criteria used for selection. A cerclage is only indicated in singleton pregnancies with previous spontaneous preterm birth and a combined cervical shortening in the current pregnancy. Nevertheless, the short-and long-term outcome has never been evaluated, whereas maternal complications may be increased. There is no evidence for a pro-phylactic cervical cerclage in twin pregnancies even in cases with cervical shortening. Emergency cerclage remains an indication after individual counseling. The effect of a cervical pes-sary in singleton pregnancy seems to be more pronounced in studies where a few investigators with increasing experience have treated and followed the patients at risk for preterm birth. Mainly in twin pregnancies, pessary treatment seems to be promising compared to other treatment options of secondary prevention when the therapy is started at early stages of precocious cervical ripening. At present, several international trials with the goal to reduce global rates of prematurity are in progress which will hopefully allow to specify the indications and methods of intervention for certain subgroups. When trials are summarized, prospective meta-analyses carry a lower risk of bias than the meanwhile uncontrolled magnitude of retrospective meta-analyses with conflicting results. GebFra Science | Review 585 Kyvernitakis I et al. Controversies about the … Geburtsh Frauenheilk 2018; 78: 585-595
... In recent years, the use of vaginal pessary has been returned to the forefront. The vaginal pessary that is used is Arabin pessary [40]. A multifactorial research in Spain proved that, in women with cervical length <25 mm in 18-22 weeks of pregnancy, the use of pessary decreased premature birth in 34 weeks of gestation by 88% and also decreased neonate complications [41]. ...
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Objective: Preterm labor is one of the most significant obstetric problems associated with high rate of actual and long-term perinatal complications. Despite the creation of scoring systems, uterine activity monitoring, cervical ultrasound and several biochemical markers, the prediction and prevention of preterm labor is still a matter of concern. The aim of this study was to examine cervical findings for the prediction and the comparative use of Arabin pessary or cerclage for the prevention of preterm birth in asymptomatic women with high risk factors for preterm labor. Material and methods: The study group was composed of singleton pregnancies (spontaneously conceived) with high risk factors for preterm labor. Cervical length, dilatation of the internal cervical os and funneling, were estimated with transvaginal ultrasound during the first and the second trimesters of pregnancy. Results: Cervical funneling, during the second trimester of pregnancy, was the most significant factor for the prediction of preterm labor. The use of Arabin cervical pessary was found to be more effective than cerclage in the prolongation of pregnancy. Conclusion: In women at risk for preterm labor, the detection of cervical funneling in the second trimester of pregnancy may help to predict preterm labor and to apply the appropriate treatment for its prevention. Although the use of cervical pessary was found to be more effective than cerclage, more studies are needed to classify the effectiveness of different methods for such prevention.
... So erhöht sich das Risiko für eine Frühgeburt bei jeder Konisation um das 5-fache und das Risiko für perinatale Mortalität um das 2,8-fache[29]. Während die Cerclage in diesen Hochrisikoschwangerschaften mit Zervixverkürzung die Frühgeburtlichkeit nicht senken konnte[30,31], wurde bei Pessareinlage im ersten Trimenon eine klinisch relevante Prolongation der Schwangerschaft beschrieben[32].Nicolaides und Mitarbeiter[33] haben in einer multikontinentalen prospektiven Studie Pessare bei Patientinnen mit Einlingsschwangerschaft und Zervixverkürzung appliziert. Die Autoren konnten keine Unterschiede zwischen Pessar-und Kontrollgruppe finden. ...
Article
Objective: Cervical funneling is associated with spontaneous preterm birth (sPTB). The aim of this analysis was to assess the relationship between funneling shape and the response to the McDonald cerclage, the Arabin pessary and the early total cervical occlusion (ETCO). Methods: We retrospectively analyzed data of 312 randomly selected singleton pregnancies with cervical shortening <25 mm or normal cervical length and evaluated them according to the progression of funneling: control group (n = 46), cervical shortening without funneling (n = 107), V-shaped funneling (n = 68), U-shaped funneling (n = 47), and prolapse of the amniotic sac (n = 44). We evaluated sPTB rates <34, <28, <32, and <37 weeks as well as prolongation of gestation and birthweight. Results: Regarding the rate of sPTB <34 weeks there was no statistical significance in either of the comparisons between control group and each of the four risk groups. Regarding prolongation of gestation we demonstrated a statistical significance for all risk groups compared to the control group (all p < .05) with the lowest prolongation rate noted in the group with amnion prolapse and the highest in the group with isolated cervical shortening without funneling. Similarly, progression of funnel shape resulted in an absolute decrease of birthweight for all risk groups compared to the control group, albeit not significant for the group with U-shaped funneling (p = .1058). Conclusion: Independent of the treatment, there was a significant impact of funneling shape on pregnancy duration and birthweight.
Article
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INTRODUCTION: We aimed to demonstrate the outcomes of cervical cerclage in order to prevent preterm births resulting in high neonatal morbidity and mortality. METHODS: The outcomes of 56 cases with McDonald cerclage application evaluated according to ACOG (American College of Obstetrics and Gynecology) criteria. The first group consisted of 32 cases in which there was no dilation in the second trimester and the second group in 24 cases with cervical dilatation less than 3 cm with cervical shortening. RESULTS: When the results of cervical cerclage were compared, it was found that the first group birth week were later (p: 0,002), the period between the cerclage and delivery was longer (p: 0,001) and birth weight were heavier (p: 0,002) than the second group. DISCUSSION AND CONCLUSION: Cervical cerclage application is a good option for to reduce recurrent pregnancy loss and preterm delivery in cervical insufficiency.
Article
Objective: To evaluate the efficacy of cervical pessary in the prevention of preterm birth and its influence on pregnancy and maternal outcomes, so as to provide a clinical basis for cervical pessary to prevent premature delivery. Method. The databases of PubMed, Web of Science, CNKI, WanFang Data, etc, were used to search for the eligible articles. The relevant data were abstracted by two independent reviewers and performed with Stata 12.0. Result. Pregnancy Result: the PTB rates of pessary and control group before 28, 32, 34 and 37 weeks were analyzed and the combined RR (95%CI) values were 0.78 (0.46, 1.31), 0.92 (0.67, 1.28), 0.74 (0.49, 1.13) and 0.79 (0.54, 1.15). Compared with the control group, the utilization rate of tocolytic and corticosteroids was decreased 21% (RR = 0.79, 95% CI = 0.66–0.94) and 18% (RR = 0.82, 95% CI = 0.70–0.96). The risk of PROM and the difference was not statistically significant (p > 0.05). Subgroup analysis showed that there was no significant difference on the PTB rate subgroup and twins subgroup during 28 and 34 weeks (p > 0.05). Neonate Results: the results showed that there was no significant difference on neonatal weight < 1500 g and < 2500 g (p > 0.05). 3 articles on the average gestational age were included in the cervical length < 25 mm. The deepen analysis on the relationship between gestational weeks and neonatal showed that: the risk of neonatal sepsis was reduced by 55% (RR = 0.45, 95% = 0.22 − 0.93); RDS and intraventricular hemorrhage are no significant difference on pessary and control group. The neonatal results were analyzed by subgroup analysis of singletons and twins, and there was no significant difference between two groups (p > 0.05).
Article
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Shunji SuzukiDepartment of Obstetrics and Gynecology, Japanese Red Cross Katsushika Maternity Hospital, Tokyo, JapanWe read the recent review article entitled “Prevention of preterm delivery: current challenges and future prospects” by van Zijl et al.1 However, they did not adequately discuss the prevention of preterm delivery in cases with a history of conization, or a cone biopsy of the uterine cervix.2,3 Performing a cervical cerclage has been common in the treatment of pregnant women with cervical insufficiency to prevent preterm delivery, as reported by van Zijl et al.1 However, the effect of prophylactic cerclage in women with a history of conization is little understood, because there are no prospective randomized controlled trials concerning the efficiency and risk of prophylactic cerclage in this subgroup of pregnant women.3–15 Table 1 summarizes the previous examinations concerning the effect of prophylactic cerclage in pregnancy after conization, including four English language articles searched using PubMed (Bethesda, MD, USA) and eight Japanese language articles searched using Igaku Chuo Zasshi® (NPO Japan Medical Abstracts society, Tokyo, Japan), with the key search terms of “cerclage” and “conization”.4–15 In these studies, statistical significances of the categorical variables were tested by Χ2 test (with Yates’s correction) or Fisher’s exact test. As shown in Table 1, there have been some small retrospective population-based cohort studies in this field. In an earlier study,3 cerclage has been recommended in pregnancies following excessive cone biopsy. However, some recent studies have suggested an association between local infection in cases of short cervices related to large cones and preterm labor in women with a history of conization.4–7 In these cases, sutures can act as a foreign body and lead to uterine irritability and contractions after a cerclage procedure.5–7 Moreover, some authors have reported a significant increase in pathologic flora in the vagina and cervix after cerclage leading to chorioamnionitis and preterm labor.16 Thus, prophylactic cerclage is used more sparingly in pregnancies following conization in recent years.5–7 Authors' replyMaud D van Zijl,1 Bouchra Koullali,1 Ben WJ Mol,2 Eva Pajkrt,1 Martijn A Oudijk11Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, the Netherlands; 2The Robinson Research Institute, School for Reproductive Health and Pediatrics, University of Adelaide, Adelaide, SA, AustraliaWe have read the response by Dr Suzuki with interest, and we agree with Dr Suzuki that our paper does not discuss preventive measures in cases with a history of conization. However, in our opinion, there is currently insufficient evidence of benefit from a cerclage in this specific group.It is known that women with a prior excisional procedure have a higher risk of preterm birth.1–3 As Dr Suzuki already points out, there are no randomized controlled trials that focus on the prevention of preterm birth in these high-risk women. So far, literature on the best strategy to prevent preterm birth after cone biopsy is lacking. Therefore, our paper does not give clear advice on how to treat these cases.View the original paper by van Zijl et al.
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Radical and repeated cone biopsies are associated with a high risk of spontaneous preterm birth. A 30-year-old gravida 1 presented with a spontaneous dichorionic twin pregnancy. She had a history of two radical surgical conizations. By speculum examination, no cervical tissue was detected. A history-indicated transabdominal cervicoisthmic cerclage was performed at 12 + 4/7 gestational weeks because of assumed cervicoisthmic insufficiency. The pregnancy continued until 34 + 3/7 weeks when the patient developed preeclampsia indicating Cesarean delivery. Transabdominal cerclage in twin pregnancy has rarely been described, but it may be considered in case of extreme cervical shortening after radical cervical surgery, as it would in singleton pregnancy.
Article
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This review describes rationale and gradual introduction of cervical pessaries into clinical practice, technical aspects of more commonly used designs and provides guidance for their use and future evaluation. Possible advantages include easy, 'one off' application, good side-effect profile, good patient tolerability and relatively low cost compared to current alternatives. Use of transvaginal sonography allows much better selection of patients that may benefit, but future clinical trials are needed to establish the clear role of pessaries as a preterm birth prevention strategy world-wide.
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To explore the association between preterm delivery and treatment at colposcopy. Retrospective-prospective cohort study using record linkage. 12 National Health Service hospitals in England. Women who had a cervical histology sample taken between 1987 and 2009. These women were linked by hospital episode statistics to hospital obstetric records between 1998 and 2009 for the whole of England to identify singleton live births between 20-43 gestational weeks before or after cervical histology. Proportion of preterm births (<37 weeks); the relative risk for the strength of association between preterm births and treatment for cervical intraepithelial neoplasia. 18,441 singleton births occurred: 4176 before histology and 14,265 after histology. Of the singleton births after histology, 9.0% (n=1284) were preterm compared with 6.7% of all births in England over the same period (excess risk 2.3 per 100 births, 95% confidence interval 1.8% to 2.8%). Among first births after histology, the adjusted relative risk associated with previous treatment was 1.19 (95% confidence interval 1.01 to 1.41); among first births before histology the relative risk associated with subsequent treatment was 1.47 (1.05 to 2.05). Combining these, the relative risk associated with treatment adjusted for timing relative to histology was 0.91 (0.66 to 1.26) corresponding to an absolute difference of -0.25 (-2.61 to 2.11) per 100 singleton births. Among 372 women who gave birth both before and after treatment, there were 30 preterm births after treatment and 32 before treatment (relative risk 0.94, 0.62 to 1.43). The risk of preterm delivery in women treated by colposcopy in England was substantially less than that in many other studies, predominantly from Nordic countries. The increased risk may be a consequence of confounding and not caused by treatment. Although this study is reassuring for large loop excision of the transformation zone overall, it is possible that deep conisation or repeated treatment leads to an increased risk of preterm delivery.
Article
Objective Assess the cost-effectiveness of a cervical pessary to prevent preterm delivery in women with a multiple pregnancy.Study designAn economic analysis alongside a randomized clinical trial evaluating cervical pessaries (ProTWIN).Women with a multiple pregnancy were included. We performed an economic evaluation from a societal perspective. Costs were estimated between randomisation and 6 weeks postpartum. We separately analysed the prespecified subgroup of women with a cervical length (CL) below the 25th percentile (<38 mm).Primary endpoint was poor perinatal outcome until 6 weeks postpartum. We estimated direct medical costs and health outcomes. We calculated incremental cost-effectiveness ratios for costs to prevent one poor outcome.ResultsMean costs in the pessary group (n = 401) were €21884 versus €22030 in the no-pessary group (n = 407) (difference -€146 (95% confidence interval (CI) €-5648 to €4718)). In the prespecified subgroup of women with a CL <38 mm we demonstrated a significant reduction of poor perinatal outcome (12% vs 29%, RR 0.40; 95% CI 0.19-0.83). The mean costs in the pessary group (n = 78) were €25142 versus €30577 in the no-pessary group (n = 55) (difference -€5436 (95% CI €-11001 to €1456). In women with CL <38 mm, pessary treatment is the dominant strategy (more effective and less costly) with a probability of 94%.Conclusion In unselected women with a multiple pregnancy treatment with a cervical pessary generates comparable costs as in women without treatment. However, using a pessary in women with a CL <38 mm results in better outcomes and lower costs.
Article
Introduction: In Germany, cost and revenue structures of hospitals with defined treatment priorities are currently being discussed to identify uneconomic services. This discussion has also affected perinatal centres (PNCs) and represents a new economic challenge for PNCs. In addition to optimising the time spent in hospital, the hospital management needs to define the "best" patient mix based on costs and revenues. Method: Different theoretical models were proposed based on the cost and revenue structures of the University Perinatal Centre for Franconia (UPF). Multi-step marginal costing was then used to show the impact on operating profits of changes in services and bed occupancy rates. The current contribution margin accounting used by the UPF served as the basis for the calculations. The models demonstrated the impact of changes in services on costs and revenues of a level 1 PNC. Results: Contribution margin analysis was used to calculate profitable and unprofitable DRGs based on average inpatient cost per day. Nineteen theoretical models were created. The current direct costing used by the UPF and a theoretical model with a 100 % bed occupancy rate were used as reference models. Significantly higher operating profits could be achieved by doubling the number of profitable DRGs and halving the number of less profitable DRGs. Operating profits could be increased even more by changing the rates of profitable DRGs per bed occupancy. The exclusive specialisation on pathological and high-risk pregnancies resulted in operating losses. All models which increased the numbers of caesarean sections or focused exclusively on c-sections resulted in operating losses. Conclusion: These theoretical models offer a basis for economic planning. They illustrate the enormous impact potential changes can have on the operating profits of PNCs. Level 1 PNCs require high bed occupancy rates and a profitable patient mix to cover the extremely high costs incurred due to the services they are legally required to offer. Based on our theoretical models it must be stated that spontaneous vaginal births (not caesarean sections) were the most profitable procedures in the current DRG system. Overall, it currently makes economic sense for level I PNCs to treat as many low-risk pregnancies and neonates as possible to cover costs.
Article
In women with a multiple pregnancy, spontaneous preterm delivery is the leading cause of perinatal morbidity and mortality. Interventions to reduce preterm birth in these women have not been successful. We assessed whether a cervical pessary could effectively prevent poor perinatal outcomes. We undertook a multicentre, open-label randomised controlled trial in 40 hospitals in the Netherlands. We randomly assigned women with a multiple pregnancy between 12 and 20 weeks' gestation (1:1) to pessary or control groups, using a web-based application with a computer-generated list with random block sizes of two to four, stratified by hospital. Participants and investigators were aware of group allocation. For women in the pessary group, a midwife or obstetrician inserted a cervical pessary between 16 and 20 weeks' gestation. Women in the control group did not receive the pessary, but otherwise received similar obstetrical care to those in the pessary group. The primary outcome was a composite of poor perinatal outcome: stillbirth, periventricular leucomalacia, severe respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, proven sepsis, and neonatal death. Analyses were by modified intention to treat. This trial is registered in the Dutch trial registry, number NTR1858. Between Sept 21, 2009, and March 9, 2012, 813 women underwent randomisation, of whom 808 were analysed (401 in the pessary group; 407 in the control group). At least one child of 53 women (13%) in the pessary group had poor perinatal outcome, compared with 55 (14%) in the control group (relative risk 0·98, 95% CI 0·69-1·39). In unselected women with a multiple pregnancy, prophylactic use of a cervical pessary does not reduce poor perinatal outcome. The Netherlands Organisation for Health Research and Development.
Article
Objective To help elucidate the mechanism of action of the Arabin cervical pessary in pregnancies at high risk for preterm delivery. Methods Cervical length and uterocervical angle were evaluated in relation to gestational age in 198 pregnancies not at high risk for preterm birth that underwent clinical fetal magnetic resonance imaging (MRI). Additionally, in 73 singleton pregnancies at high risk for preterm birth, an Arabin cervical pessary was placed at 14-33 weeks' gestation. We performed MRI of the cervix immediately before and after placement and at monthly follow-up until removal of the pessary. In a subgroup of 54 pregnancies with a short cervix and pessary placement at 17-31 weeks' gestation, the uterocervical angle and cervical length at follow-up were compared with the preplacement values. ResultsIn pregnancies not at high risk for preterm birth, the uterocervical angle did not vary, but cervical length showed a significant decrease with gestational age (r = -0.15, P < 0.05). Among the high-risk patients, the cervical pessary was successfully placed at first attempt in 60 (82.2%) and by the second attempt in 66 (90.4%), remaining well positioned until removal. In five patients we failed to place the pessary after two attempts, in one patient the pessary dislodged during follow-up and in one case the pessary was partly placed in the external cervical canal and triggered labor the next day. Among the subgroup of 54 patients, the median uterocervical angle immediately after pessary placement was significantly more acute than that prior to placement in the 46 (85.2%) who delivered after 34 weeks (132 degrees vs 146 degrees, P < 0.01), but was unchanged in the eight patients who delivered before 34 weeks (143 degrees vs 152 degrees, P > 0.05). Conclusion In patients at high risk for preterm delivery, correct placement of the Arabin cervical pessary should be checked immediately; this can be performed quickly and easily using MRI. This study provides some evidence that, in singleton pregnancies with a short cervix, a cervical pessary delays birth through a mechanical effect on the uterocervical angle. Copyright (c) 2013 ISUOG. Published by John Wiley & Sons Ltd.