In this retrospective study, we found that mifepristone combined with ethacridine lactate account for the majority of still induction in the third-trimester in our hospital and it is a safe and effective induction method for patients with stillbirth in the third-trimester.
In our hospital, the induction methods of stillbirth in the third-trimester in our hospital have no unified method in different Obstetrical units. Also, different doctors might also choose different induction methods for stillbirth in the third-trimester. After excluding patients with contraindications, such as those with abnormal liver function, drug allergy, etc., the cervical maturity degree by Bishop might be the main consideration in choosing the induction method. When the cervix is unfavorable, mifepristone combined with ethacridine lactate account for the majority of still induction in the third-trimester in our hospital was widely used, though exogenous prostaglandins or mechanical methods that stimulate release of endogenous prostaglandins to “ripen” the cervix could also be employed and it was reported that intracervical Foley’s catheter is popular in resource-constrained settings,[13] however, in our hospital Foley’s catheter or Cock balloon was used preferred in those women after the induction failure at the first time. Artificial amniotomy alone or combined with oxytocin may be used when the cervix is favorable as reported.[14] When the induction process exceeded 72 hours was considered induction failure, further measures would be taken. In our study, there were 3 cases resulting in induction failure and they were all in the mifepristone combined with ethacridine lactate group, who were 32 gestational weeks plus 1 day, 30 gestational weeks, and 28 gestational weeks plus 2 days. In these three cases, one failure case was added another 75mg ethacridine lactate and delivered, one were subsequently accepted oxytocin intravenous drip and delivered in the next day, and the other one accepted intravaginal misoprostol 400mg twice and delivered.
Overcoming the unfavorable cervix, however, remains the most challenging task in induction of labor. Consequently, development of safe and cost-effective agents to ripen the cervix and induce contractions remains a major research issue.[15] Formulations of prostaglandin E2 (PGE2) administered vaginally are accepted as the gold standard for labor induction.[16] As the guideline recommended, in the event of an intrauterine fetal death, if there is evidence of ruptured membranes, infection or bleeding, offer immediate induction of labor or cesarean birth. If a woman choose an induced labor, offer oral mifepristone 200mg followed by vaginal dinoprostone or oral or vaginal misoprostol, or a mechanical method of induction.[12] After intrauterine fetal death, women with a scarred uterus are at increased risk of uterine rupture and should be taken into account when considering options for birth and if the induction is carried out.[12]In our study, there were 3 women appeared with complications in ethacridine lactate group, mainly presented as hemorrhage in two women and hematuria in one woman. The two women who suffered from postpartum hemorrhage were both subsequent to induction failure, with hemorrhage 560ml and 630ml, respectively, and mainly secondary to uterine atony.The woman with hematuria had no history of cesarean section or uterine surgery, and the reason of hematuria was unclear, with normal B-ultrasound scanning of the pelvic organs, she had a rapid recovery after conservative treatment, including bladder irrigation. Compared with the international guidelines, the reason why misoprostol is not widely used in China might result from the lack of low-dose misoprostol. High dose misoprostol may cause uterine rupture.
In our study, there were four cases who were performed artificial amniotomy (+ Oxytocin), among whom two cases suffered from hemorrhage (850ml and 1500ml, respectively) for placental abruption, one case suffered from rectal injury for macrosomia(4015g) and had a rectal repair with the help of surgeon. Despite of the small number of cases, it seemed that the method of artificial amniotomy had a high rate of complications(75%, 3/4).
There were some strength in our study. First, the report of ethacridine lactate used in stillbirth induction in the third trimester has enriched the evidences of induction in clinic. Second, we found that 50mg ethacridine lactate had similar effect as 75mg or 100mg in the induction of the late pregnancy. Lower the dosage of ethacridine lactate may reduce potential adverse outcomes. However, several limitations should also be noted. First, this study was a hospital-based retrospective study, and the incomplete variables might result in statistical bias. Second, the number of the cases included in this study was limited, which resulted in difficulties for further analysis. Third, because the lack of unified guideline, the indications and dosages of ethacridine lactate used in stillbirth induction during the third-trimester remains inexplicit, which might partially affect the outcomes.
In conclusion, our study confirms mifepristone combined with ethacridine lactate is a safe and effective induction method for patients with stillbirth in the third-trimester. Further research on ethacridine lactate may help to broaden the applications of the medicine in clinics and improve the induction outcomes of stillbirth, and relieve the mom and dad's painful experiences.