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.