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\begin{document}

\title{Evaluation of the efficacy of vaginal progesterone in preventing preterm
birth after abdominal trachelectomy: a prospective study with a
historical cohort}



\author[1]{Yuka Sato}%
\author[1]{Nobuhiro Hidaka}%
\author[1]{Atsuhiko Sakai}%
\author[1]{Saki Kido}%
\author[1]{Yasuyuki Fujita}%
\author[1]{Kaoru Okugawa}%
\author[2]{Hideaki  Yahata}%
\author[2]{Kiyoko Kato}%
\affil[1]{Kyushu University Faculty of Medicine Graduate School of Medical Sciences School of Medicine}%
\affil[2]{Kyushu University}%


\vspace{-1em}



  
  \date{May 22, 2024}


\begingroup
\let\center\flushleft
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\selectlanguage{english}
\begin{abstract}
Objective To determine whether vaginal progesterone (VP) reduces the
rate of preterm birth in pregnant women after abdominal trachelectomy
(AT) for early-stage cervical cancer Design Prospective cohort study
with a historical cohort Setting University hospital Population Twelve
pregnancies in ten women were included in the VP group between October
2016 and September 2020. By contrast, 19 pregnancies in 17 women were
included in the historical control group between January 2007 and
September 2016. Methods For the interventional study participants, the
administration of vaginal progesterone was started between 16+0 and 19+6
weeks of gestation and discontinued at 34 weeks of gestation or at the
time of delivery, rupture of membranes, or massive uterine bleeding,
whichever occurred first. We investigated obstetric and neonatal
outcomes among the study participants and compared them with outcomes of
the historical control group participants. Main Outcome Measures The
gestational age at delivery and incidence of preterm birth before 37
weeks and 34 weeks of gestation Results The incidence of preterm birth
at \textless{}37 weeks was 10/12 (83\%) in the VP group and 11/19 (58\%)
in the control group, and the incidence of preterm birth at
\textless{}34 weeks was 6/12 (50\%) in the VP group and 9/19 (47\%) in
the control group. The incidence of preterm birth in the two groups was
similar, and the difference between the two groups was not statistically
significant. Conclusions The administration of vaginal progesterone did
not reduce the rate of preterm birth among pregnant women after AT.%
\end{abstract}%



\sloppy


Title: Evaluation of the efficacy of vaginal progesterone in preventing
preterm birth after abdominal trachelectomy: a prospective study with a
historical cohort

Yuka Sato,\emph{yuka-s@med.kyushu-u.ac.jp}, Department of Obstetrics and
Gynecology, Graduate School of Medical Sciences, Kyushu University,
Fukuoka, Japan

Nobuhiro Hidaka,\emph{nhidaka1120sylphy@yahoo.co.jp}, Department of
Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu
University, Fukuoka, Japan / Department of Obstetrics, Fukuoka
Children's Hospital, Fukuoka, Japan

Atsuhiko Sakai, atsuhiko12241983@yahoo.co.jp, Department of Obstetrics
and Gynecology, Graduate School of Medical Sciences, Kyushu University,
Fukuoka, Japan

Saki Kido,\emph{sakking55@yahoo.co.jp}, Department of Obstetrics and
Gynecology, Graduate School of Medical Sciences, Kyushu University,
Fukuoka, Japan

Yasuyuki Fujita,\emph{yfujita@med.kyushu-u.ac.jp}, Department of
Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu
University, Fukuoka, Japan

Kaoru Okugawa,\emph{kokugawa@med.kyushu-u.ac.jp}, Department of
Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu
University, Fukuoka, Japan

Hideaki Yahata,\emph{hyahata@med.kyushu-u.ac.jp}, Department of
Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu
University, Fukuoka, Japan

Kiyoko Kato,\emph{kkato@med.kyushu-u.ac.jp}, Department of Obstetrics
and Gynecology, Graduate School of Medical Sciences, Kyushu University,
Fukuoka, Japan

Correspondence: Yuka Sato, Department of Obstetrics and Gynecology,
Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi,
Higashi-ku, Fukuoka 812-8582, Japan.

E-mail: yuka-s@med.kyushu-u.ac.jp

Phone: +81 92 642 5395; Fax: +81 92 642 5414

\textbf{Running title}

Progesterone to prevent post-AT preterm birth



\textbf{{[}Abstract{]}}

\textbf{Objective}

To determine whether vaginal progesterone (VP) reduces the rate of
preterm birth in pregnant women after abdominal trachelectomy (AT) for
early-stage cervical cancer

\textbf{Design}

Prospective cohort study with a historical cohort

\textbf{Setting}

University hospital

\textbf{Population}

Twelve pregnancies in ten women were included in the VP group between
October 2016 and September 2020. By contrast, 19 pregnancies in 17 women
were included in the historical control group between January 2007 and
September 2016.

\textbf{Methods}

For the interventional study participants, the administration of vaginal
progesterone was started between 16\textsuperscript{+0} and
19\textsuperscript{+6} weeks of gestation and discontinued at 34 weeks
of gestation or at the time of delivery, rupture of membranes, or
massive uterine bleeding, whichever occurred first. We investigated
obstetric and neonatal outcomes among the study participants and
compared them with outcomes of the historical control group
participants.

\textbf{Main Outcome Measures}

The gestational age at delivery and incidence of preterm birth before 37
weeks and 34 weeks of gestation

\textbf{Results}

The incidence of preterm birth at \textless{}37 weeks was 10/12 (83\%)
in the VP group and 11/19 (58\%) in the control group, and the incidence
of preterm birth at \textless{}34 weeks was 6/12 (50\%) in the VP group
and 9/19 (47\%) in the control group. The incidence of preterm birth in
the two groups was similar, and the difference between the two groups
was not statistically significant.

\textbf{Conclusions}

The administration of vaginal progesterone did not reduce the rate of
preterm birth among pregnant women after AT.

\textbf{Funding}

None

\textbf{Keywords}

abdominal trachelectomy, vaginal progesterone, preterm birth, preterm
premature rupture of membranes

\textbf{Tweetable abstract}

Vaginal progesterone did not reduce the preterm birth rate among
pregnant women after abdominal trachelectomy.

\textbf{{[}Introduction{]}}

Abdominal trachelectomy (AT) has been used as a fertility-sparing
surgery for early-stage cervical cancer in women of reproductive age
since the first report (Smith JR, 1997) on the same was
published,\textsuperscript{1} and is defined as surgical removal of the
uterine cervix with preservation of the uterine body. The incidence of
cervical cancer in reproductive-aged women is
increasing,\textsuperscript{2-4} and the number of women desiring
pregnancy after AT is also increasing accordingly. Many reports on
obstetric outcomes in pregnant women after AT in the past have described
the high risk of miscarriage, preterm birth, and preterm premature
rupture of membranes (pPROM).\textsuperscript{5-9} The reported
incidence of preterm birth and miscarriage ranges from 53\% to
89\%,\textsuperscript{6-10} and the high rate of complications in
pregnant women after AT can be attributed to the loss of the supporting
tissue of the cervical canal that maintains pregnancy and ascending
infection due to the loss of the cervical mucus plug. Although the high
risk of miscarriage has recently been well recognized, a preventive
approach for pregnancies after AT has not been discussed.

The efficacy of progesterone administration in preventing preterm birth
in high-risk pregnant women such as those with a history of preterm
birth\textsuperscript{11,12} or women with a shortened
cervix\textsuperscript{13,14} has recently been established, and the use
of this drug for managing such high-risk pregnancies has become common
in Western countries.\textsuperscript{15,16} The mechanism of\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}action of
progesterone\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}responsible
for\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}preventing\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}preterm\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}birth\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}has\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}not\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}been\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}fully\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}determined,\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}but\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}the
preventive effect is\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}speculated\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}to be caused by its anti-inflammatory
effect, decreased cervical stromal degradation, and a decreased
frequency of contractions of the myometrium.\textsuperscript{17} The
efficacy of progesterone in preventing preterm birth in high-risk
pregnancies is unquestioned; however, to the best of our knowledge, the
use of progesterone for reducing the risk of preterm birth in pregnant
women after AT has not been reported to date.

Against this background, we designed an interventional study to
determine\begin{CJK}{UTF8}{gbsn}　\end{CJK}\selectlanguage{english}whether vaginal progesterone (VP) reduces the rate of preterm
birth in pregnant women after AT.

\textbf{{[}Methods{]}}

\textbf{Study population and design}

This was a prospective interventional study that commenced in October
2016. The Kyushu University Hospital Ethical Review Board approved the
study, and all work was conducted in accordance with the Declaration of
Helsinki (1964). The enrollment criterion was women with singleton
pregnancies after the second trimester who had previously undergone AT
for early-stage uterine cervical cancer at our hospital. The exclusion
criteria were abortion during early pregnancy, contraindications for
progesterone use, multiple pregnancies, women who had undergone AT in
other hospitals, and fetuses with severe anomalies or abnormal
chromosomes. Eligible women were invited to participate in this study
and sign a consent form. After obtaining informed consent, we started
vaginal progesterone administration.

The primary outcomes of our study were gestational age at delivery and
the incidence of preterm birth before 37 weeks and 34 weeks of
gestation. The secondary outcomes were the incidence of pPROM and other
obstetric complications, maternal adverse events (transfusion for
massive vaginal bleeding, hysterectomy after cesarean section, septic
shock, and maternal death), and neonatal morbidity and perinatal
mortality (fetal death and neonatal death). We investigated these
outcomes among the study participants and compared them with those of
the historical control group participants. The historical control group
included women with singleton pregnancies after AT who were managed
without VP at our institution between January 2007 and September 2016.
Data of the historical control group participants were collected
retrospectively by reviewing both maternal and neonatal medical records
of each participant. In 2017, we reported the perinatal outcomes of
singleton pregnancies after AT\textsuperscript{18} managed between March
2005 and October 2015, and the historical control group in this study
partly overlapped with that reported in the previous study.

\textbf{Administration of vaginal progesterone}

For the study participants, administration of vaginal progesterone was
started between 16\textsuperscript{+0} and 19\textsuperscript{+6} weeks
of gestation. We used 200 mg vaginal progesterone capsules (UTROGESTAN\selectlanguage{ngerman}®
vaginal capsules 200 mg, Fuji Pharma Co., Ltd., Japan). The women
self-administered the tablets vaginally once daily at night.
Progesterone administration was discontinued at 34 weeks of gestation or
at the time of delivery, rupture of membranes, or massive uterine
bleeding, whichever occurred first. At approximately 26 weeks of
gestation, study participants were examined for side effects of
progesterone through the following blood tests: (1) liver function:
aspartate aminotransferase {[}AST{]} and alanine aminotransferase
{[}ALT{]} and (2) coagulation function: D-dimer, and further tests were
conducted if the test results were abnormal.

\textbf{Institutional management policy for pregnancies after abdominal
trachelectomy}

We checked for the presence of vaginal varices at the uterovaginal
anastomotic site. Pregnant women after AT were routinely hospitalized
after 30 weeks for anticipated acute bleeding from vaginal varices. The
mode of delivery was determined as cesarean section and planned at 37
weeks of gestation if the pregnancy progressed uneventfully. Cesarean
section was routinely performed because a permanent cervical cerclage
was placed during abdominal trachelectomy.

If threatened preterm delivery due to frequent uterine contractions was
suspected on cardiotocography, tocolytic agents including oral calcium
channel blockers (Ca-blockers), intravenous magnesium sulfate, or
ritodrine were administered as required. When pPROM occurred prior to 34
weeks of gestation, antenatal corticosteroids, and prophylactic
antibiotics (ampicillin and clindamycin) were administered. When the
pregnancies reached 34 weeks of gestation without spontaneous labor
onset or development of clinical chorioamnionitis (cCAM) even after
pPROM, a cesarean section was performed at 34 weeks of gestation. If
labor commenced or cCAM was diagnosed during expectant management of
pPROM, a cesarean section was immediately performed. cCAM was diagnosed
by an axillary temperature \textgreater{}38.0 °C and at least one of the
following signs: heart rate \textgreater{}100 bpm, serum white blood
cell count \textgreater{}15,000/\selectlanguage{greek}µ\selectlanguage{english}L, and C-reactive protein level of
\textgreater{}2.0 mg/dL. When pPROM occurred after 34 weeks of
gestation, a prompt cesarean delivery was performed.

\textbf{Statistical analysis}

Non-normally distributed data are reported as median and range. We
compared the two groups using Fisher's exact test for categorical
variables and the Mann--Whitney U-test for continuous variables. A
p-value \textless{}0.05 was considered statistically significant.
Statistical analyses were performed using SPSS Statistics for Windows,
version 21.0 (IBM Corp., Armonk, NY).

\textbf{{[}Results{]}}

During the study period, 12 pregnancies in ten women were included in
the VP group. In contrast, 19 pregnancies in 17 women were included in
the historical control group. Results from the comparison of the
oncological background characteristics of the ten women in the VP group
and 17 women in the historical control group, and the baseline maternal
characteristics of the 12 pregnancies in the VP group and 19 pregnancies
in the historical control group are shown in Table 1. The cancer stage
and operative procedures were similar in the two groups. Age at delivery
and the rate of assisted reproductive technology use were similar
between the two groups; one egg donation-embryo transfer was noted in
the VP group. The median duration between surgery and delivery was
somewhat longer in the VP group than in the control group, but the
difference was not statistically significant.

Table 2 shows the pregnancy and perinatal outcomes. The incidence of
preterm birth at \textless{}37 weeks was 10/12 (83\%) in the VP group
and 11/19 (58\%) in the control group, and the incidence of preterm
birth at \textless{}34 weeks was 6/12 (50\%) in the VP group and 9/19
(47\%) in the control group. The difference in the incidence of preterm
birth between the two groups was similar and not statistically
significant. The most common cause of preterm emergency cesarean section
was pPROM in both groups. Figure 1 shows the distribution of gestational
age at delivery in both groups. The median gestational age at delivery
was 33\textsuperscript{+6} weeks (range: 26\textsuperscript{+0} to
37\textsuperscript{+4} weeks) in the VP group and
34\textsuperscript{+6}weeks (range: 23\textsuperscript{+5} to
37\textsuperscript{+5} weeks) in the control group. No miscarriages
(delivery \textless{}22 weeks) occurred in either group. The incidence
of pPROM was 6/12 (50\%) in the VP group and 8/19 (42\%) in the control
group. The median gestational age at pPROM tended to be earlier in the
VP group than in the control group, although the difference was not
statistically significant. In the VP group, intrauterine fetal death
occurred at 32 weeks of gestation in one case. The fetal anatomic survey
was unremarkable, and the cause of fetal death was undetermined. Other
pregnancy and perinatal outcomes were similar between the two groups.

Table 3 shows the maternal adverse events. Of the total number of
pregnant women, abnormal massive vaginal bleeding from vaginal or
cervical varices during pregnancy occurred in eight women, and three
women from the VP group and four from the control group required blood
transfusion. In the control group, total abdominal hysterectomy (TAH)
after cesarean section was performed in two women. The indications for
TAH were placenta accreta in one and septic shock due to the development
of an intra-abdominal abscess following cesarean section in another. In
the VP group, no side effects of progesterone were noted.

Table S1 shows the neonatal outcomes of the 30 liveborn infants. In the
control group, an infant death occurred in one case. The birth weight,
number of admissions to the Neonatal Intensive Care Unit, and other
neonatal outcomes were similar in the two groups. Of the study
participants, 17 infants have already reached 1.5 years of corrected
age. Regarding neurodevelopmental outcomes, in the control group,
cerebral palsy was noted in one of the infants. None of the infants had
mental retardation or epilepsy.

\textbf{{[}Discussion{]}}

\textbf{Main findings}

Our study suggested that vaginal progesterone was ineffective in
preventing preterm birth in pregnant women after AT. The incidence of
preterm birth at \textless{}34 weeks and at \textless{}37 weeks and
gestational age at delivery were similar between the VP and control
groups.

\textbf{Strengths and Limitations}

This is the first interventional study to investigate the prevention of
preterm birth in pregnant women after AT and describe the obstetric and
antepartum complications in detail. One limitation of our study was the
absence of randomization. However, the study groups were separated by a
time period, and clinicians could not use their discretion to determine
whether vaginal progesterone should be administered. Therefore, we
believe that the backgrounds in both groups were similar and that our
study has a certain level of precision as a comparison analysis. Another
limitation was the small sample size. Initially, we had planned to
accumulate data from a larger sample size for a longer study period;
however, based on the apparently ineffective results presented herein,
the only alternative was to stop this interventional study early,
considering that any study in a clinical setting should be performed on
behalf of patients.

\textbf{Interpretation}

Our study showed a high incidence of preterm birth (58\%) in the control
group (without VP), and the median gestational age at delivery was 34
weeks. These findings were consistent with those of previous studies
analyzing obstetrical outcomes of pregnant women after
AT.\textsuperscript{3-7} Furthermore, the incidence of pPROM in the
control group was 42\%, which was the main cause of preterm birth.
Preterm birth in pregnant women after AT is believed to be due to the
loss of the supporting tissue of the cervical canal that maintains
pregnancy and ascending infection resulting from the loss of the
cervical mucus plug, which may contribute to
pPROM.\textsuperscript{19}Complications associated with prematurity may
greatly impair the development and quality of life of a preterm infant,
even after long-term survival; therefore, it is important that obstetric
clinicians make consecutive efforts to prevent preterm birth. Based on
these findings, we conducted this study to administer progesterone
supplements to pregnant women who had undergone AT in anticipation of
its preventive effect on preterm birth.

Progesterone plays an important role in the maintenance of pregnancy.
Circulating levels of progesterone rise during pregnancy, and
destruction of the corpus luteum, the main source of progesterone during
early pregnancy, leads to spontaneous abortion/miscarriage. There is
convincing evidence regarding its role in reducing the incidence of
preterm birth. Progesterone includes natural progesterone administered
vaginally (vaginal progesterone) and
17-alpha-hydroxy-progesterone-caproate (17-OHP) administered
intramuscularly. Vaginal progesterone and 17-OHP are both considered
effective in preventing preterm birth, and both have been administered
to eligible pregnant women at high risk of preterm
birth.\textsuperscript{11,20}

It remains controversial whether 17-OHP or vaginal progesterone is more
effective in preventing preterm birth in women with a history of preterm
birth. Some studies\textsuperscript{11,12} have found 17-OHP to be
superior in this regard, and the American College of Obstetricians and
Gynecologists (ACOG)\textsuperscript{21} and the Society for Maternal
Fetal Medicine (SMFM)\textsuperscript{17} recommend the use of the
former. On the other hand, some studies\textsuperscript{22,23} have
suggested vaginal progesterone to be superior, and the Society of
Obstetricians and Gynecologists of Canada (SOGC) guidelines recommend
the use of vaginal progesterone.\textsuperscript{24} In Japan, data
regarding this drug is still lacking, and it has not been recommended by
the guidelines. In this study, we selected vaginal progesterone as it
could be inserted by the women themselves, and we expected to achieve
favorable medication compliance. However, the administration of vaginal
progesterone did not reduce the preterm birth rate in our study, and the
incidence of pPROM and histologic chorioamnionitis (hCAM; stage
\textgreater{}II) did not decrease. The mechanisms of action of
progesterone responsible for preventing preterm birth are believed to
include its anti-inflammatory effects, ability to reduce cervical
stromal degradation, and ability to inhibit myometrial
contractions,\textsuperscript{16,17} but these mechanisms remain to be
fully determined. The negative data presented herein suggest that the
presence of the uterine cervix is essential for vaginal progesterone to
exert a preventive effect on preterm birth.

On the other hand, seven women required blood transfusion due to massive
bleeding from cervical varices and two underwent TAH after cesarean
section due to antepartum complications. In particular, two of the seven
women who required blood transfusion went into preterm labor because of
the massive bleeding (at 28 weeks and 34 weeks). We have previously
discussed the significance of vaginal and cervical varices in the
management of pregnancies after trachelectomy,\textsuperscript{18} and
we speculated that venous pressure could increase during pregnancy,
inducing varix formation at the uterovaginal anastomotic site. Although
the management of vaginal and cervical varices in pregnant women after
AT needs to be discussed further,\textsuperscript{7} we believe that
variceal bleeding may also induce preterm labor, and it should be
recognized as an important complication in the management of pregnancy
after AT.

\textbf{Conclusion}

The administration of vaginal progesterone did not reduce the rate of
preterm birth among pregnant women after AT. This negative result
suggests that the existence of the uterine cervix is essential for the
preventive effect of progesterone on preterm birth.

\textbf{{[}Acknowledgements{]}}

We are grateful to the neonatology team of Kyushu University Hospital
for providing neonatal intensive care and follow-up.

\textbf{{[}Disclosure of Interests{]}}

None declared; the completed disclosure of interests from is available
online as supporting information.

\textbf{{[}Contribution to Authorship{]}}

Y.S., N.H., and K.K. conceived the study. Y.S. and N.H. carried out data
research and wrote the manuscript. A.S., S.K., Y.F., K.O., H.Y., and
K.K. contributed to the discussion and reviewed the manuscript.

\textbf{{[}Details of Ethics Approval{]}}

This study was approved initially by the Kyushu University Institutional
Review Board for Clinical Trials, Fukuoka, Japan, Aug. 5, 2016 (Trial
ID: UMIN000023161). However, the Clinical Trials Act came into force in
Japan, April 2018. By the new act, all clinical trials which correspond
to the legal requirements have been required to be registered to the new
official database ``jRCT''. Therefore, this study was reviewed again and
approved by the Kyushu University Certified Institutional Review Board
for Clinical Trials which has been established by the new act, March 29,
2019 (Trial ID: jRCTs071180085).

\textbf{{[}Funding{]}}

None



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assistance of Vincenzo Berghella. Progesterone and preterm birth
prevention: translating clinical trials data into clinical
practice.\emph{Am J Obstet Gynecol.} 2012;206:376-86.

18. Okugawa K, Kobayashi H, Sonoda K, et al. Oncologic and obstetric
outcomes and complications during pregnancy after fertility-sparing
abdominal trachelectomy for cervical cancer: a retrospective
review.\emph{Int J Clin Oncol.} 2017;22:340-6.

19. Ebisawa K, Takano M, Fukuda M, et al. Obstetric outcomes of patients
undergoing total laparoscopic radical trachelectomy for early stage
cervical cancer. \emph{Gynecol Oncol.} 2013;131:83-6.

20. Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone
reduces the rate of preterm birth in women with a sonographic short
cervix: a multicenter, randomized, double-blind, placebo-controlled
trial. \emph{Ultrasound Obstet Gynecol.} 2011;38:18-31.

21. Society for Maternal Fetal Medicine Publications Committee. ACOG
Committee Opinion number 419 October 2008 (replaces no. 291, November
2003). Use of progesterone to reduce preterm birth. \emph{Obstet
Gynecol.} 2008;112:963-5.

22. Winer N, Bretelle F, Senat MV, et al. 17 alpha-hydroxyprogesterone
caproate does not prolong pregnancy or reduce the rate of preterm birth
in women at high risk for preterm delivery and a short cervix: a
randomized controlled trial. \emph{Am J Obstet
Gynecol.}2015;212:485.e1-10.

23. Maher MA, Abdelaziz A, Ellaithy M, Bazeed MF. Prevention of preterm
birth: a randomized trial of vaginal compared with intramuscular
progesterone. \emph{Acta Obstet Gynecol Scand.} 2013;92:215-22.

24. Jain V, McDonald SD, Mundle WR, Farine D. Guideline No. 398:
progesterone for prevention of spontaneous preterm birth. \emph{J
Obstetr Gynaecol Can.} 2020;42:806-12.

\textbf{Table captions}

Table 1. Oncological background of 27 women who underwent abdominal
trachelectomy and maternal characteristics of 31 pregnant women\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
Total\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
VP group\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
Control group\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
P-value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Oncological backgraound\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N=27\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N=10\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N=17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Age at operation (years old)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
32 (26-39)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
32 (26-38)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
31 (26-39)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Cancer stage\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
CIN3\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
IA2\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (12)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
IB1\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
22 (81)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7 (70)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15 (88)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
IB2\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Histology\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Adenocarcinoma\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11 (41)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (40)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7 (41)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Squamous cell carcinoma\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
14 (52)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (30)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
10 (59)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Adenosquamous carcinoma\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
CIN3\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (20)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Operative procedure\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
AST\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
AmRT\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
12 (44)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (50)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7 (41)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
ART\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
13 (48)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (40)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
9 (53)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Maternal characteristics\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N=31\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N=12\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N=19\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Age at delivery (years old)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
37 (28-45)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
38 (30-45)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
36 (28-41)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Primipara\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
21 (68)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7 (58)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
14 (74)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
ART\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
19 (61)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8 (67)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11 (58)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
IVF\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
12 (39)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (42)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7 (37)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
ICSI\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6 (19)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (21)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Egg donation-ET\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Duration between surgery and delivery (months)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
46 (13- 133)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
56 (13-133)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
43 (16-105)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Data are presented as the number (\%) or median (range)

VP, vaginal progesterone; CIN, cervical intraepithelial neoplasia; AST,
abdominal simple trachelectomy; AmRT, abdominal modified radical
trachelectomy; ART, abdominal radical trachelectomy; ART, assisted
reproductive technology; IVF, in vitro fertilization; ICSI,
intracytoplasmic sperm injection; ET, embryo transfer; N.S., not
significant

Table 2. Pregnancy and perinatal outcomes\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Perinatal outcomes\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Total N=31\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
VP group N=12\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Control group N=19\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
P-value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
GA at delivery (weeks)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
34\textsuperscript{+0}
(23\textsuperscript{+5}-37\textsuperscript{+5})\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
33\textsuperscript{+3}
(26\textsuperscript{+0}-37\textsuperscript{+4})\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
34\textsuperscript{+6}
(23\textsuperscript{+5}-37\textsuperscript{+5})\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Miscarriage (\textless{}22 weeks)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Preterm birth\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
21 (68)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
10 (83)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11 (58)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}28 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
[?]28 weeks, \textless{} 34 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
12 (39)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (42)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7 (37)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
[?]34 weeks, \textless{} 37 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6 (19)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (33)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
pPROM\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
14 (45)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6 (50)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8 (42)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
GA at pPROM (weeks)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
30\textsuperscript{+3}
(23\textsuperscript{+5}-35\textsuperscript{+1})\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
28\textsuperscript{+1}
(24\textsuperscript{+5}-34\textsuperscript{+0})\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
32\textsuperscript{+1}
(23\textsuperscript{+5}-35\textsuperscript{+1})\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Clinical CAM\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Histological CAM\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (16)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Stage I\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Stage II\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Stage III\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (16)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (16)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
IUFD\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Reason for preterm birth\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
cCAM\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
PROM\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7 (23)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (26)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Labor onset\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (13)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Bleeding from varices\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (16)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Presumed fetal compromise\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (17)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Data are presented as the number (\%) or median (range)

GA, gestational age; VP, vaginal progesterone; TPL, threatened premature
labor; pPROM, preterm premature rupture of membranes; cCAM, clinical
chorioamnionitis; IUFD, intrauterine fetal death; CS, cesarean section;
N.S., not significant Table 3. Maternal adverse events\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Total (N=31)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
VP group (N=12)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
Control group (N=19)\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
P-value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Abnormal vaginal bleeding from varix\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8 (26)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5 (26)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Blood transfusion during pregnancy\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7 (23)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3 (25)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4 (21)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Sepsis\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1 (5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TAH\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (7)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2 (11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Death\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0 (0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
N.S.\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Data are presented as the number (\%) or median (range)

VP, vaginal progesterone; TAH, total abdominal hysterectomy; N.S., not
significant

\textbf{Figure captions}

Figure 1. Distribution of gestational age at delivery

VP: vaginal progesterone

Supporting information, Table 1. Neonatal outcomes of the 30 liveborn
infants

Data are presented as the number (\%) or median (range)

VP, vaginal progesterone; NICU, neonatal intensive care unit; RDS,
respiratory distress syndrome; CLD, chronic lung disease; NEC,
necrotizing enterocolitis; IVH, intraventricular hemorrhage; PVL,
periventricular leukomalacia; DQ, developmental quotient; CP, cerebral
palsy;

N.S., not significant

\textbf{Hosted file}

\verb`Figure_1.docx`  available at \url{https://authorea.com/users/468070/articles/561920-evaluation-of-the-efficacy-of-vaginal-progesterone-in-preventing-preterm-birth-after-abdominal-trachelectomy-a-prospective-study-with-a-historical-cohort}

\selectlanguage{english}
\FloatBarrier
\end{document}

