Prophylactic cervical cerclage is performed in pregnant women with a medical history of previous typical spontaneous abortion associated with cervical insufficiency. The use of the medical history is insufficient to diagnose cervical insufficiency in pregnant women with true cervical insufficiency8,9.
In the present study, prophylactic cerclage was significantly associated with term birth; nevertheless, a history of preterm birth was not significantly associated with the occurrence of preterm birth and abortion. Although we could not evaluate whether pregnant women who underwent prophylactic cerclage truly had cervical insufficiency, prophylactic cerclage should be considered as a promising therapy for cervical insufficiency diagnosed using a typical medical history.
Preterm birth was significantly reduced after therapeutic cerclage among high-risk pregnant women with a history of preterm birth10. Therapeutic cerclage reduces neonatal morbidity and mortality in pregnant women having a history of spontaneous preterm birth with gestational age < 34 weeks, or in women with ongoing singleton pregnancies having a CL less than 25 mm at a gestational age < 24 weeks11. Further, therapeutic cerclage is reportedly effective in pregnant women with a CL ≤\(\)10 mm having no preterm birth history, albeit not effective in women with singleton pregnancies having no preterm birth history and with a CL ≤\(\)25 mm5. According to a Japanese randomized controlled trial (RCT), the gestational period was not significantly prolonged after therapeutic cerclage; however, the proportion of patients requiring preterm birth management was significantly reduced in pregnant women with a short CL ≤\(\)25.0 mm who underwent therapeutic cerclage between 16- and 26-week gestations12. In contrast to these previous study findings, several studies have reported negative effects of therapeutic cerclage in pregnant women with a shortened CL and without a preterm birth history13. Thus, there is no established consensus regarding the clinical indications for therapeutic cervical cerclage.
In the present study, therapeutic cerclage was significantly associated with preterm birth and abortion. Obviously, the outcome of therapeutic cerclage is worse than that of prophylactic cerclage. However, therapeutic cerclage is not a useless therapy for women with cervical insufficiency diagnosed during an ongoing pregnancy. The principal new finding of this study is that therapeutic cerclage is a promising therapeutic strategy for pregnant women with cervical insufficiency having a pre-cerclage CL ≥ 17 mm, as it produces a long-term pregnancy sustenance > 13 weeks post-cerclage. However, therapeutic cerclage is effective only in pregnant women with a pre-cerclage CL ≤ 10 mm and without a history of preterm birth5. In a previous study, a cerclage group, having pregnant women with CL ≤ 15 mm at 22 to 24 weeks' gestation, had fewer preterm births before 32 weeks of gestation compared with a non-cerclage group13. We do not know the exact reason for this discrepancy between our findings and previous study findings. The abovementioned discrepancy may have been influenced by the difference in outcomes of successful cervical cerclage and indications of therapeutic cerclage between the studies.
Guideline for Obstetrical Practice in Japan 2020 recommend the measurement of WBC and serum CRP levels before cervical cerclage, as cervicitis and intrauterine infection can render cerclage ineffective14. Furthermore, high pre-cerclage cervical interleukin 8 (IL-8) levels significantly increase the rate of preterm birth, and cerclage exerts a counterproductive effect on pregnancy outcomes in women with subclinical cervicitis associated with high IL-8 levels15.
All patients in our study had normal pre-cerclage WBC and CRP levels, which were not significantly associated with preterm birth, abortion, and unsuccessful cervical cerclage. The pre-cerclage WBC and CRP levels were normal range in all patients because physicians abided by Guideline for Obstetrical Practice in Japan 202014. Cervical IL-8 levels were not measured in our study population. Eighty-seven percent of pregnant women with normal WBC and CRP levels and pre-cerclage CL \(\ge\)17 mm sustain their pregnancies for > 13 weeks post-cerclage; hence, it may be unnecessary to measure cervical IL-8 levels before cerclage.
ROC curve analysis in the present study revealed that 64% of patients having pre-cerclage CL < 17 mm sustained their pregnancies for up to 13 weeks post-cerclage. Thus, pregnant women with severely shortened pre-cerclage CL are likely to have a preterm birth, even if the cerclage procedure is performed appropriately. The use of Arabic pessary, in addition to cervical cerclage, is reportedly an option for preventing preterm birth in patients with CL less than the third percentile16,17. A previous study reported that, in addition to cervical cerclage, the use of vaginal progesterone in women with shortened CL < 10 mm significantly decreases overall spontaneous preterm birth rates and overall neonatal morbidity and mortality. Moreover, the same study showed that the average pregnancy latency was 14 weeks in patients who underwent a combination of cerclage and vaginal progesterone administration; there was a two-fold prolongation in the pregnancy latency period with respect to that of patients who received only vaginal progesterone18. Thus, additional treatments such as the use of Arabic pessary and vaginal progesterone may contribute to better pregnancy outcomes.
This study had three serious limitations. First, this study was not an RCT; therefore, the true efficacy of therapeutic cerclage was not adequately verified. Second, we defined efficacious cerclage as one that enabled the maintenance of pregnancy for at least 13 weeks; hence, the pregnancy outcomes may be different if different definitions of efficacious cerclage are used. Lastly, as described in the introduction, physicians in the four perinatal medical centers might have performed therapeutic cerclage for different indications (i.e., with differential degrees of uterine contraction before cerclage), as there is no well-established clinical indication for therapeutic cerclage.