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.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.19Complications 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.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 studies11,12 have found 17-OHP to be
superior in this regard, and the American College of Obstetricians and
Gynecologists (ACOG)21 and the Society for Maternal
Fetal Medicine (SMFM)17 recommend the use of the
former. On the other hand, some studies22,23 have
suggested vaginal progesterone to be superior, and the Society of
Obstetricians and Gynecologists of Canada (SOGC) guidelines recommend
the use of vaginal progesterone.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
>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,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,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,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.