The results of this study indicated that different methods of terminating pregnancy in the second trimester of hydatidiform mole coexisting with a normal fetus were feasible, and the main complications included massive blood loss and progression to GTN. The incidence of massive blood loss (over 300ml) was 50.0%. Molar tissues closer to the lower uterine segment than the fetus (P = 0.035), and presence of complications (P = 0.015) were the risk factors for massive blood loss during termination of pregnancy. The incidence of progression to GTN was 35.7%. Further researches were needed to investigate the correlation between different termination methods of pregnancy and complications such as massive blood loss and progression to GTN. Forceps curettage, intra-amniotic injection of rivanol, and cesarean section all posed risks of massive blood loss and progression to GTN.
In clinical practice, there was controversy on whether to continue or terminate pregnancy after diagnosing hydatidiform mole coexisting with a normal fetus. It was generally believed that when the fetus in the uterus was a live fetus with a normal karyotype, pregnancy could be continued under close monitoring[6, 7]. Diploid karyotype, few and focal extent of hydatidiform tissue, low rate of molar degeneration, and the absence of fetal anemia hypothesized as the factors that influenced survival of the fetus[8]. When women decided to continue their pregnancy, a multidisciplinary team consisting of obstetricians, experts in maternal and child medicine, gynecological oncologists, and neonatologists should be involved in the patient's care[9]. According to a literature review, the average gestational age for twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus was 34 weeks, and the live birth rate increased year by year, from 6.7% in 2000, 33.3% in 2012, to 50% in 2017[9]. Hydatidiform mole coexisting with a normal fetus was a high-risk pregnancy with high incidences of complications, including vaginal bleeding, pre-eclampsia, hyperthyroidism, preterm delivery, intrauterine fetal death and progression to GTN[10]. Some studies had shown that low serum hCG level was the best indicator to predict fetal survival rate (P = 0.006), and serum hCG level lower than 400000 IU/L was a good candidate for continuing pregnancy and achieving fetal survival[11]. However, termination of pregnancy seemed to be a safe option in patients with serious complications, high serum hCG levels or suspected lung metastasis.
Little researches were retrieved from literature on the volume of blood loss during the termination of pregnancy in the second trimester of hydatidiform mole coexisting with a normal fetus. The results of this study indicated that there was a risk of massive blood loss in various termination methods, including forceps curettage, intra-amniotic injection of rivanol and cesarean section. The incidence of blood loss over 300ml was 50.0%. Molar tissues closer to the lower uterine segment than the fetus and presence of complications were the risk factors. More studies were warranted on the correlation between volume of blood loss and the size of hydatidiform mole, serum hCG level. For patients with high risk of massive blood loss, it was necessary to closely monitor the amount of blood loss, and more medical measures should be taken to prevent and reduce the volume of bleeding. Prophylactic bilateral uterine artery embolization was reasonable for some selected patients.
There was a risk of progression to GTN after termination of pregnancy in the second trimester of hydatidiform mole coexisting with a normal fetus. The risk of progression to post-molar GTN was about 15–20% of patients in complete hydatidiform mole and 1.5% in partial hydatidiform mole[12, 13]. The risk of progression to GTN in hydatidiform mole coexisting with a normal fetus was higher than that of single complete moles[14]. A multi-center study showed that the overall incidence of GTN after hydatidiform mole coexisting with a normal fetus was 46%[15]. Compared with patients with natural remission, patients with GTN showed higher levels of hCG (250000 IU/L vs 120000 IU/L, p = 0.026) and higher rates of termination of pregnancy due to complications (20% vs 0%, p = 0.006)[15]. A literature review summarized 36 patients of singleton normal fetus with partial hydatidiform mole, and the incidence of GTN was 25.0%[16]. Compared with termination of pregnancy at less than 24 weeks of gestation, over 24 weeks of gestation was a protective factor for GTN[16], and the authors believed that in addition to uncontrolled severe complications, pregnancy could continue without increasing the risk of GTN progression. In this study, the incidence of progression to GTN after termination in second trimester was 35.7%, and its risk factors still required larger sample sized studies.
There was a lack of researches on the methods of termination of pregnancy in the second trimester of hydatidiform mole coexisting with a normal fetus[17]. Some scholars suggested that there was controversy over the intra-amniotic injection of rivanol and intravenous injection of oxytocin in the second trimester[18], as repeated uterine contractions might increase the likelihood of hydatidiform mole tissue being compressed into the abdominal cavity and consequently increased the risk of tumor metastasis. Some scholars had also suggested that medication termination (rivanol or misoprostol) might increase the risk of excessive bleeding[19]. For young patients with fertility desires, cesarean section increased the risk of uterine scars, making it a difficult choice for physicians and patients. In 2019, Zhang summarized the cases of hydatidiform mole coexisting with a normal fetus[19]. In the report, 3 patients receiving medication termination all progressed to GTN, while 2 patients receiving surgical termination did not progressed to GTN. The authors believed that cesarean section might be a safer treatment strategy[19], and Wang held similar opinion[20]. However, results of this larger sample size study showed that the risk of progression to GTN after medication termination was not higher than that after surgical termination. Different termination methods, including forceps curettage, intra-amniotic injection of rivanol, and cesarean section, all posed risks of progression to GTN. The risk might be related to the characteristics of hydatidiform mole, while the correlation with the termination methods was not yet clear.
Strengths and limitations
To our knowledge, this study was the first single center based, relatively large sample sized study that focused on the safety of different termination methods in the second trimester of hydatidiform mole coexisting with a normal fetus. Secondly, data from several patients in this study confirmed that the risk of progression to GTN after medication termination (combination of mifepristone and misoprostol, and intra-amniotic injection of rivanol), was not higher than that after surgical termination (forceps curettage and cesarean section). Thirdly, in this study, we found that the risk of massive blood loss was high in the termination of hydatidiform mole coexisting with a normal fetus in the second trimester. Molar tissues closer to the lower uterine segment than the fetus and presence of complications were the risk factors.
Since the limited number of patients with hydatidiform mole coexisting with a normal fetus, the sample size of this study might not be sufficient to analyze the correlation between complications, such as massive blood loss and progression to GTN, and possible risk factors, including the size of the hydatidiform mole, serum hCG levels and termination methods. Secondly, this study involved a long time span of 18 years, and advances in medical monitoring and treatment methods might have impacts on the volume of bleeding. Thirdly, this study was a retrospective study, and its conclusions still needed to be confirmed in prospective studies.