Safety of different termination methods for hydatidiform mole coexisting with a normal fetus in the second trimester

Safety of different termination methods for hydatidiform mole coexisting with a normal fetus in the second trimester | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Safety of different termination methods for hydatidiform mole coexisting with a normal fetus in the second trimester Guorui Zhang, Weilin Chen, Ping Peng, Li Jin, Xinyan Liu, Chunying Li, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4625376/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: To explore the safety of different termination methods of hydatidiform mole coexisting with a normal fetus in the second trimester of pregnancy. Methods: This is a retrospective cohort study conducted in a referral center for difficult and critical diseases in Obstetrics and Gynecology in Beijing, China. Patients diagnosed hydatidiform mole coexisting with a normal fetus who received termination of pregnancy in the second trimester (12 weeks to 27 +6 weeks) were enrolled. The primary end point was the safety of different termination methods, including the volume of blood loss and progression to gestational trophoblastic neoplasm. Results: Different methods of terminating pregnancy in the second trimester of hydatidiform mole coexisting with a normal fetus were feasible, including forceps curettage, combination of mifepristone and misoprostol, intra-amniotic injection of rivanol, and cesarean section. 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 gestational trophoblastic neoplasm was 35.7%. Conclusion: Different termination methods might lead to complications including massive blood loss and progression to gestational trophoblastic neoplasm. More medical measures should be taken to prevent and reduce the volume of bleeding among patients with high risk factors. Hydatidiform mole coexisting with a normal fetus termination complication massive blood loss progression to gestational trophoblastic. Figures Figure 1 Background Hydatidiform mole coexisting with a normal fetus referred to the coexistence of hydatidiform mole and a normal fetus. It was first described by Laker in 1914, with an incidence of 1/22000 to 1/100000[ 1 ]. There were three types of hydatidiform mole coexisting with a normal fetus: twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus, twin pregnancies combining a partial hydatidiform mole coexisting with a normal fetus, and singleton normal fetus with partial hydatidiform mole. In order to make a definite diagnosis, ultrasonography in the first trimester, placental pathology examination, chromosome examination, and even p57KIP2 immunohistochemical staining were needed. Hydatidiform mole coexisting with a normal fetus was usually diagnosed in the late first trimester or the second trimester. The most common clinical symptom was vaginal bleeding. Patients usually presented with more significant uterine enlargement and higher human chorionic gonadotropin (hCG) levels, compared with that of the corresponding gestational age. Complications including hyperthyroidism, pre-eclampsia, hyperemesis, luteinized ovarian cysts, and progression to gestational trophoblastic tumors (GTN) might also occur[ 2 ]. With the development of assisted reproductive technology, the twin pregnancy rate had significantly increased, and pregnant women with twin pregnancy had the risk of gestational trophoblastic disease (one of the gestational sacs was complete hydatidiform mole or partial hydatidiform mole)[ 3 ]. The number of patients with hydatidiform mole coexisting with a normal fetus was larger than before[ 4 ], raising more severe challenges to their clinical management. Due to the limited number of clinical cases, there was a lack of high-quality evidence to support the recommendation whether to continue or to terminate the pregnancy when patients are diagnosed with hydatidiform mole coexisting with a normal fetus. A systematic review summarized 244 patients diagnosed with twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus in 14 studies[ 5 ]. Among 182 patients who continued pregnancy, the live birth rate was 50% (91/182), the pre-term birth rate was 78% (71/91), and the intrauterine fetal death rate was 40.1% (73/182). Among them, the incidence of maternal complications was as high as 80.8% (147/182), including 70.5% (91/129) of vaginal bleeding, 23.3% (30/129) of hyperthyroidism, 14.3% (26/182) of preeclampsia, and 34% (83/244) of progression to GTN, specifically[ 5 ]. There was currently limited research on the methods of termination of pregnancy in the second trimester when serious complications occurred or patients requested termination due to concerns about adverse outcomes. The study aimed to explore the safety of different termination methods of hydatidiform mole coexisting with a normal fetus in the second trimester of pregnancy. Methods Study design This study was a single center based retrospective study. Patients diagnosed and treated in Peking Union Medical College Hospital from January 2005 to December 2023 were enrolled. The inclusion criteria were: A) diagnosis of hydatidiform mole coexisting with a normal fetus, including twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus, twin pregnancies combining a partial hydatidiform mole coexisting with a normal fetus, and singleton normal fetus with partial hydatidiform mole; B receiving termination of pregnancy in the second trimester (12 weeks to 27 + 6 weeks). After the diagnosis of hydatidiform mole coexisting with a normal fetus was suspected by ultrasonography, the patient received consultations from obstetricians, maternal and infant medical experts, and gynecological oncologists. A decision to terminate the pregnancy was made when serious complications (including massive vaginal bleeding, severe pre-eclampsia, and suspected GTN) occurred, or the patient requested termination of pregnancy due to concerns about adverse outcomes. Methods of termination was determined based on the patient's gestational age and general condition, and full informed consent. The methods included forceps curettage, combination of mifepristone and misoprostol, intra-amniotic injection of rivanol, and cesarean section. Medical records of the included patients were retrospectively collected and the patients were followed up for one year after termination of pregnancy. All patients received serum hCG test and fetus and placenta imaging examination within one week before termination of pregnancy. Based on the ultrasonography or magnetic resonance imaging before termination of pregnancy, it was determined whether molar tissues was closer to the lower segment of the uterus compared with the fetus (Fig. 1 ). Assessment on symptoms and complications related to hydatidiform mole was performed, including vaginal bleeding, hyperthyroidism, pre-eclampsia, luteinized ovarian cysts and GTN. This study was approved by the Institutional Review Board of Peking Union Medical College Hospital, and informed consent was obtained from study participants. Variables and definitions The primary end point of this study was the safety of different termination methods, including the volume of blood loss and progression to GTN. The volume of blood loss referred to the bleeding from the beginning of termination to 24 hours after placental discharge, excluding the volume of spontaneous vaginal bleeding before termination of pregnancy. Massive blood loss was defined that the amount of bleeding was greater than 300ml. Progression to GTN was diagnosed by gynecological oncology experts, based on changes of serum hCG levels and imaging examination. The secondary endpoint was the success rate of different termination methods. Statistical analysis SPSS22.0 was used for data analysis, and chi square analysis was used to compare the differences between groups for categorical variables. Unilateral P < 0.05 was considered statistically significant. Results Patients characteristics A total of 14 patients were enrolled in this study, including 11 patients of twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus, and 3 patients of singleton normal fetus with partial hydatidiform mole. The median age of all patients at the time of termination of pregnancy was 29 years old (range, 23–37 years old), and the median gestational age was 17.5 weeks (range, 12–26 weeks). The serum hCG levels in 7 patients before terminating pregnancy was higher than 8 × 10 5 IU/L, and in 3 patients were between 4 × 10 5 IU/L and 8 × 10 5 IU/L. In terms of indications for terminating pregnancy, 3 patients terminated their pregnancy due to maternal complications, including massive vaginal bleeding in 1 patient, severe pre-eclampsia in 1 patient, and diagnosis of invasive hydatidiform mole because of lung metastasis in 1 patient; 2 patients terminated their pregnancy due to intrauterine fetal death; and 9 patients requested for terminating pregnancy for concerns about adverse outcomes. Methods of terminating pregnancy and major complications All 14 patients were divided into 4 groups according to the methods of terminating pregnancy, as following: A) forceps curettage group, 3 patients; B) combination of mifepristone and misoprostol group, 2 patients; C) intra-amniotic injection of rivanol group, 4 patients; and D) cesarean section group, 5 patients. The general conditions of the 14 patients were shown in Table 1 , and the characteristics of patients in different groups were summarized below. Table 1 The detailed characteristics of enrolled patients Patient Age, years old Gestational age, weeks The largest diameter of hydatidiform mole, cm complications Serum hCG level, IU/L Types Indications for terminating pregnancy Molar tissues closer to lower segment of the uterus than the fetus Methods of termination Change termination method Volume of blood during termination, ml Progression to GTN 1 27 14 12.1×12.4 No 1.0×10 6 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Request for termination Yes Forcep curettage No 100 Yes, chemotherapy 1 month after termination 2 37 11 5.0×3.1 No 2.5×10 5 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Request for termination No Forcep curettage No 50 No 3 28 14 18.5×10.8 Hyperthyroidism, vaginal bleeding, bilateral ovarian luteinized cyst 3.5×10 6 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Request for termination Yes Forcep curettage No 2500 Yes, chemotherapy 2 month after termination 4 35 16 14.0×12.1 No 6.1×10 5 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Request for termination Yes Combination of mifepristone and misoprostol No 200 No 5 35 14 5.6×2.5 No 1.4×10 5 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Request for termination No Combination of mifepristone and misoprostol No 100 No 6 23 26 13.0×10.2 Invasive hydatidiform mole, intrauterine fetal death 2.2×10 5 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Intrauterine fetal death Yes Intra-amniotic injection of rivanol Change to esarean section due to massive bleeding 1100 Yes, chemotherapy immediately after termination 7 27 19 10.1×5.2 No 4.1×10 5 Singleton normal fetus with partial hydatidiform mole Request for termination No Intra-amniotic injection of rivanol No 100 No 8 27 19 16.3×15.5 Hyperthyroidism 8.8×10 5 Singleton normal fetus with partial hydatidiform mole Request for termination Yes Intra-amniotic injection of rivanol No 2100 No 9 31 23 10.5×6.7 No 1.0×10 5 Singleton normal fetus with partial hydatidiform mole Intrauterine fetal death No Intra-amniotic injection of rivanol No 100 No 10 29 17 19.7×16.8 Severe pre-eclampsia 8.5×10 5 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Pre-eclampsia Yes Cesarean section No 1200 No 11 33 16 18.4×16.2 Pre-eclampsia 3.3×10 6 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Request for termination Yes Cesarean section No 700 No 12 23 18 6.0×5.0 Respiratory failure, invasive hydatidiform mole, vaginal bleeding, bilateral ovarian luteinized cyst 2.3×10 6 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Invasive hydatidiform mole Yes Cesarean section No 400 Yes, chemotherapy immediately after termination 13 34 18 15.2×7.3 No 6.8×10 5 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Request for termination Yes Cesarean section No 400 No 14 29 18 16.0×11.4 Vaginal bleeding 1.7×10 6 Twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus Vaginal bleeding Yes Cesarean section No 100 Yes, chemotherapy 18 days after termination Abbreviations: hCG, human chorionic gonadotropin; GTN, gestational trophoblastic neoplasm. A) Forceps curettage group 3 patients underwent curettage, with gestational ages of 11–14 weeks. The maximum diameters of hydatidiform moles were 5.0-18.5 cm. The hCG levels in 2 patients were > 8 × 10 5 IU/L. The molar tissues in 2 patients were closer to the lower segment of the uterus compared with the fetus. Massive blood loss occurred in 1 patient (2500 ml) and progression to GTN occurred in 2 patients. B) Combination of mifepristone and misoprostol group 2 patients were administered combination of mifepristone and misoprostol to terminate pregnancy, with gestational ages of 14–16 weeks. The maximum diameters of hydatidiform moles were 5.6–14.0 cm. The hCG levels in 2 patients were less than 8 × 10 5 IU/L. The molar tissue in 1 patient was closer to the lower segment of the uterus compared with the fetus. The 2 patients underwent curettage after the discharge of fetus and hydatidiform mole. No massive blood loss and no progression to GTN occurred. C) Intra-amniotic injection of rivanol group 4 patients underwent intra-amniotic injection of rivanol, with gestational ages of 19–26 weeks. The maximum diameters of hydatidiform moles were 10.1–16.3 cm. The hCG level in 1 patient was > 8 × 10 5 IU/L. The molar tissues in 2 patients were closer to the lower segment of the uterus compared with the fetus. Successful induction was achieved in 3 patients, and the termination method changed to cesarean section in 1 patient due to massive blood loss during the termination process. Massive blood loss occurred in 2 patients (1100 ml, 2100ml) and progression to GTN occurred in 1 patient. D) Cesarean section group 5 patients underwent cesarean section, with gestational ages of 16–18 weeks. The maximum diameters of hydatidiform moles were 6.0-19.7 cm. The hCG levels in 4 patients were > 8 × 10 5 IU/L. The molar tissues in 5 patients were closer to the lower segment of the uterus compared with the fetus. Massive blood loss occurred in 4 patients (400ml, 400ml, 700ml, 1200ml) and progression to GTN occurred in 2 patients. Massive blood loss Among all 14 patients, 7 patients had massive blood loss during termination of pregnancy, with an incidence of 50.0%. The comparison between patients with massive blood loss and without massive blood loss was shown in Table 2 . Among the 7 patients with massive blood loss, the maximum diameters of hydatidiform mole were over 15 cm in 5 patients; serum hCG levels were over 8 × 10 5 IU/L in 5 patients; molar tissues were closer to the lower segment of the uterus than the fetus in 7 patients; and hydatidiform mole related complications were found in 6 patients. Results of this study showed that molar tissues closer to lower segment of the uterus than the fetus (P = 0.035) and presence of complications (P = 0.015) were risk factors for massive blood loss during termination of pregnancy. The correlation between serum hCG level > 8 × 10 5 IU/L, the maximum diameter of hydatidiform mole > 15cm, and the risk of massive blood loss during termination of pregnancy needed further study. Table 2 Comparison between patients with massive blood loss and without massive blood loss. Characteristics Massive blood loss (n = 7) Without massive blood loss (n = 7) P value The maximum diameter of hydatidiform mole > 15cm 5/7 1/7 0.051 Serum hCG level > 8 × 10 5 IU/L 5/7 2/7 0.143 Molar tissues closer to the lower segment of the uterus than the fetus 7/7 3/7 0.035 Presence of complications 6/7 1/7 0.015 Abbreviations: hCG, human chorionic gonadotropin The incidence of massive blood loss in medication termination group (combination of mifepristone and misoprostol, and intra-amniotic injection of rivanol) was not lower than that in surgical termination group (forceps curettage and cesarean section) (P = 0.296) (Table 3 ). The relationship between different termination methods and risk of massive blood loss needed to be clarified in larger sample size study. Table 3 Comparison of major complications between the medication termination group and the surgical termination group Complications The medication termination group (n = 6) The surgical termination group (n = 8) P value Massive blood loss 2 6 5 8 0.296 Progression to GTN 1 6 4 8 0.238 Abbreviations: GTN, gestational trophoblastic neoplasm. Progression to GTN Among all 14 patients, progression to GTN was confirmed in 5 patients, with an incidence of 35.7%. 2 patients were diagnosed invasive hydatidiform mole based on lung compute tomography before termination of pregnancy, and 3 were diagnosed invasive hydatidiform mole within 2 months after termination. The comparison between patients with progression to GTN and without progression to GTN was shown in Table 4 . Among the 5 patients with progression to GTN, the maximum diameters of hydatidiform mole were over 15 cm in 2 patients; serum hCG levels were over 8 × 10 5 IU/L in 4 patients; molar tissues were closer to the lower segment of the uterus than the fetus in 5 patients; and hydatidiform mole related complications were found in 4 patients. The risk factors for progression to GTN after termination in the second trimester still needed to be confirmed in further researches. Table 4 Comparison between patients with progression to GTN and without progression to GTN. Characteristics Progression to GTN (n = 5) Without progression to GTN (n = 9) P value The maximum diameter of hydatidiform mole > 15cm 2/5 3/9 0.657 Serum hCG level > 8 × 10 5 IU/L 4/5 2/9 0.133 Molar tissues closer to the lower segment of the uterus than the fetus 5/5 5/9 0.126 Presence of complications 4/5 3/9 0.133 Abbreviations: hCG, human chorionic gonadotropin; GTN, gestational trophoblastic neoplasm. In terms of the methods of termination of pregnancy (Table 3 ), in the medication therapy group, including combination of mifepristone and misoprostol and intra-amniotic injection of rivanol, 1 out of 6 patients progressed to GTN (1 patient diagnosed GTN before termination of pregnancy); while in the surgical group, including forceps curettage and cesarean section, 4 out of the 8 patients progressed to GTN (1 patient diagnosed GTN before termination of pregnancy). The risk of progression to GTN was not different between the medication therapy group and the surgical group. Discussion 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. Conclusions Different methods of terminating pregnancy in the second trimester of hydatidiform mole coexisting with a normal fetus were feasible, including forceps curettage, combination of mifepristone and misoprostol, intra-amniotic injection of rivanol, and cesarean section. Different termination methods might lead to complications including massive blood loss and progression to GTN. The incidence of massive blood loss was high, and molar tissues closer to the lower uterine segment than the fetus and presence of complications were risk factors. Further researches were needed to investigate the risk factors for progression to GTN. Declarations Acknowledgement None. Author contributions Conception and design: GZ, WC, PP; provision of study materials or patients: GZ, WC, LJ, XL, CL, LT, JZ, XW, YX; data analysis and interpretation: GZ, WC, PP; manuscript writing: GZ, WC; manuscript revision: PP, XL, CL, LT ;all authors have read and agreed to the final version of the paper. Funding Supported by National High Level Hospital Clinical Research Funding, No. 2022-PUMCH-A-232. Data availability The original contributions presented in the study are included in the article, and further inquiries can be directed to the corresponding authors. Ethics approval and consent to participate This study was approved by the Institutional Review Board of Peking Union Medical College Hospital, and informed consent was obtained from study participants. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. References Warton EM, Dickinson JE, White SW, et al. 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A twin pregnancy with partial hydatidiform mole and a coexisting normal fetus delivered at term: A case report and literature review. Case Rep Womens Health. 2023;39:e00544. Lee SW, Kim MY, Chung JH, et al. Clinical findings of multiple pregnancy with a complete hydatidiform mole and coexisting fetus. J Ultrasound Med. 2010;29(2):271-80. Santoso DPJ, Anton A, Nugrahani AD, et al. Partial hydatidiform mole and coexistent live fetus with placenta previa: a case report. Ann Med Surg (Lond). 2023;85(5):2020-3. Wang G, Cao J, Xu X, et al. Delivery management of a complete hydatidiform mole and co-existing viable fetus: A meta-analysis and systematic review. J Gynecol Obstet Hum Reprod. 2022;51(1):102269. Kihara M, Usui H, Tanaka H, et al. Complicating preeclampsia as a predictor of poor survival of the fetus in complete hydatidiform mole coexistent with twin fetus. J Reprod Med. 2012;57(7-8):325-8. Suksai M, Suwanrath C, Kor-Anantakul O, et al. 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Risk factors for gestational trophoblastic neoplasia development of singleton normal fetus with partial hydatidiform mole pregnancy: A retrospective cohort and literature review. J Obstet Gynaecol Res. 2023;49(2):479-86. Peng M, Li L, Zheng J, et al. Termination of twin pregnancies with hydatidiform moles: a case series of four patients. Iran J Public Health. 2014;43(7):1000-6. Aguilera M, Rauk P, Ghebre R, et al. Complete hydatidiform mole presenting as a placenta accreta in a twin pregnancy with a coexisting normal fetus: case report. Case Rep Obstet Gynecol. 2012;2012:405085. Zhang RQ, Zhang JR, Li SD. Termination of a partial hydatidiform mole and coexisting fetus: A case report. World J Clin Cases. 2019;7(20):3289-95. Wang Y, Qian H, Wang J. Medical termination of a partial hydatidiform mole and coexisting fetus during the second trimester: A case report. Oncol Lett. 2015;10(6):3625-8. Additional Declarations No competing interests reported. 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Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYDACCQgpw8bAfADESiBaCw8bA1sCSVoYeIDIgDgt/LObjz3mqbDg4ZPu+faYN8cuj4H97AH8ltw5lm7McwboMJmz2415tyUXM/Dk4bfJQCLHTDq3DahFInebNO+2A4kNEhAX4tGS/0069x9IS84zYrXksEnnNoC1sBGnReJGmpn0n2MgLWnmhnO3JSe28eTg18I/I/mZ5IyaOjl5IOPB2212if3sZ/BrQQZsSCRJWkbBKBgFo2AUoAMALlk5D+HEPhEAAAAASUVORK5CYII=","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":true,"prefix":"","firstName":"Weilin","middleName":"","lastName":"Chen","suffix":""},{"id":327620379,"identity":"a47bee67-432c-4483-bcaf-ad540c687cb7","order_by":2,"name":"Ping Peng","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Peng","suffix":""},{"id":327620380,"identity":"507fc384-8343-40e8-b841-de125160ae6b","order_by":3,"name":"Li Jin","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Jin","suffix":""},{"id":327620381,"identity":"67cfcc05-c06d-4b1c-8b7f-30e43859cd06","order_by":4,"name":"Xinyan Liu","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xinyan","middleName":"","lastName":"Liu","suffix":""},{"id":327620382,"identity":"918571ff-5faf-44af-8c7f-05d0153b8dfd","order_by":5,"name":"Chunying Li","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chunying","middleName":"","lastName":"Li","suffix":""},{"id":327620383,"identity":"b5253c4a-3ce9-4d06-af2d-d7a586f4ab5e","order_by":6,"name":"Lirong Teng","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lirong","middleName":"","lastName":"Teng","suffix":""},{"id":327620384,"identity":"c0b198b3-5952-4cf1-b2b3-e49d64bd4146","order_by":7,"name":"Jun Zhao","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Zhao","suffix":""},{"id":327620385,"identity":"82eaf841-57e4-4bc6-a666-1ff0ddb44fc6","order_by":8,"name":"Xirun Wan","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xirun","middleName":"","lastName":"Wan","suffix":""},{"id":327620386,"identity":"3b8821e5-ce90-4a01-b633-1b7bfa64af84","order_by":9,"name":"Yang Xiang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Xiang","suffix":""}],"badges":[],"createdAt":"2024-06-23 13:24:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4625376/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4625376/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60712183,"identity":"43c71c86-d688-426a-9fbf-07108f0a518d","added_by":"auto","created_at":"2024-07-19 20:24:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1059040,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRelative position relationship between molar tissue and normal fetus and placenta\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe magnetic resonance images of a 34-year-old patient at 18 weeks of gestational age showed that the molar tissue (marked with the red curve) was closer to the lower segment of the uterus compared with the normal fetus and placenta (marked with the green curve) in the sagittal plane (A) and the coronal plane (B).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4625376/v1/c541ba0129b9882cb0283935.png"},{"id":95524886,"identity":"3f589e17-69ce-4b8d-9a09-8fdb8aa51aab","added_by":"auto","created_at":"2025-11-10 10:03:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2132955,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4625376/v1/4fc956a0-c901-42d7-8e75-12147a1d0f18.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety of different termination methods for hydatidiform mole coexisting with a normal fetus in the second trimester","fulltext":[{"header":"Background","content":"\u003cp\u003eHydatidiform mole coexisting with a normal fetus referred to the coexistence of hydatidiform mole and a normal fetus. It was first described by Laker in 1914, with an incidence of 1/22000 to 1/100000[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. There were three types of hydatidiform mole coexisting with a normal fetus: twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus, twin pregnancies combining a partial hydatidiform mole coexisting with a normal fetus, and singleton normal fetus with partial hydatidiform mole. In order to make a definite diagnosis, ultrasonography in the first trimester, placental pathology examination, chromosome examination, and even p57KIP2 immunohistochemical staining were needed. Hydatidiform mole coexisting with a normal fetus was usually diagnosed in the late first trimester or the second trimester. The most common clinical symptom was vaginal bleeding. Patients usually presented with more significant uterine enlargement and higher human chorionic gonadotropin (hCG) levels, compared with that of the corresponding gestational age. Complications including hyperthyroidism, pre-eclampsia, hyperemesis, luteinized ovarian cysts, and progression to gestational trophoblastic tumors (GTN) might also occur[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. With the development of assisted reproductive technology, the twin pregnancy rate had significantly increased, and pregnant women with twin pregnancy had the risk of gestational trophoblastic disease (one of the gestational sacs was complete hydatidiform mole or partial hydatidiform mole)[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The number of patients with hydatidiform mole coexisting with a normal fetus was larger than before[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], raising more severe challenges to their clinical management.\u003c/p\u003e \u003cp\u003eDue to the limited number of clinical cases, there was a lack of high-quality evidence to support the recommendation whether to continue or to terminate the pregnancy when patients are diagnosed with hydatidiform mole coexisting with a normal fetus. A systematic review summarized 244 patients diagnosed with twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus in 14 studies[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Among 182 patients who continued pregnancy, the live birth rate was 50% (91/182), the pre-term birth rate was 78% (71/91), and the intrauterine fetal death rate was 40.1% (73/182). Among them, the incidence of maternal complications was as high as 80.8% (147/182), including 70.5% (91/129) of vaginal bleeding, 23.3% (30/129) of hyperthyroidism, 14.3% (26/182) of preeclampsia, and 34% (83/244) of progression to GTN, specifically[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. There was currently limited research on the methods of termination of pregnancy in the second trimester when serious complications occurred or patients requested termination due to concerns about adverse outcomes. The study aimed to explore the safety of different termination methods of hydatidiform mole coexisting with a normal fetus in the second trimester of pregnancy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis study was a single center based retrospective study. Patients diagnosed and treated in Peking Union Medical College Hospital from January 2005 to December 2023 were enrolled. The inclusion criteria were: A) diagnosis of hydatidiform mole coexisting with a normal fetus, including twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus, twin pregnancies combining a partial hydatidiform mole coexisting with a normal fetus, and singleton normal fetus with partial hydatidiform mole; B receiving termination of pregnancy in the second trimester (12 weeks to 27\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks).\u003c/p\u003e \u003cp\u003eAfter the diagnosis of hydatidiform mole coexisting with a normal fetus was suspected by ultrasonography, the patient received consultations from obstetricians, maternal and infant medical experts, and gynecological oncologists. A decision to terminate the pregnancy was made when serious complications (including massive vaginal bleeding, severe pre-eclampsia, and suspected GTN) occurred, or the patient requested termination of pregnancy due to concerns about adverse outcomes. Methods of termination was determined based on the patient's gestational age and general condition, and full informed consent. The methods included forceps curettage, combination of mifepristone and misoprostol, intra-amniotic injection of rivanol, and cesarean section. Medical records of the included patients were retrospectively collected and the patients were followed up for one year after termination of pregnancy. All patients received serum hCG test and fetus and placenta imaging examination within one week before termination of pregnancy. Based on the ultrasonography or magnetic resonance imaging before termination of pregnancy, it was determined whether molar tissues was closer to the lower segment of the uterus compared with the fetus (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Assessment on symptoms and complications related to hydatidiform mole was performed, including vaginal bleeding, hyperthyroidism, pre-eclampsia, luteinized ovarian cysts and GTN. This study was approved by the Institutional Review Board of Peking Union Medical College Hospital, and informed consent was obtained from study participants.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eVariables and definitions\u003c/h2\u003e \u003cp\u003eThe primary end point of this study was the safety of different termination methods, including the volume of blood loss and progression to GTN. The volume of blood loss referred to the bleeding from the beginning of termination to 24 hours after placental discharge, excluding the volume of spontaneous vaginal bleeding before termination of pregnancy. Massive blood loss was defined that the amount of bleeding was greater than 300ml. Progression to GTN was diagnosed by gynecological oncology experts, based on changes of serum hCG levels and imaging examination. The secondary endpoint was the success rate of different termination methods.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eSPSS22.0 was used for data analysis, and chi square analysis was used to compare the differences between groups for categorical variables. Unilateral P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatients characteristics\u003c/h2\u003e \u003cp\u003eA total of 14 patients were enrolled in this study, including 11 patients of twin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus, and 3 patients of singleton normal fetus with partial hydatidiform mole. The median age of all patients at the time of termination of pregnancy was 29 years old (range, 23\u0026ndash;37 years old), and the median gestational age was 17.5 weeks (range, 12\u0026ndash;26 weeks). The serum hCG levels in 7 patients before terminating pregnancy was higher than 8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L, and in 3 patients were between 4 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L and 8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L. In terms of indications for terminating pregnancy, 3 patients terminated their pregnancy due to maternal complications, including massive vaginal bleeding in 1 patient, severe pre-eclampsia in 1 patient, and diagnosis of invasive hydatidiform mole because of lung metastasis in 1 patient; 2 patients terminated their pregnancy due to intrauterine fetal death; and 9 patients requested for terminating pregnancy for concerns about adverse outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMethods of terminating pregnancy and major complications\u003c/h2\u003e \u003cp\u003eAll 14 patients were divided into 4 groups according to the methods of terminating pregnancy, as following: A) forceps curettage group, 3 patients; B) combination of mifepristone and misoprostol group, 2 patients; C) intra-amniotic injection of rivanol group, 4 patients; and D) cesarean section group, 5 patients. The general conditions of the 14 patients were shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, and the characteristics of patients in different groups were summarized below.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe detailed characteristics of enrolled patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026times;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026times;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge, years old\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGestational age, weeks\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThe largest diameter of hydatidiform mole, cm\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecomplications\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSerum hCG level, IU/L\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTypes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eIndications for terminating pregnancy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMolar tissues closer to lower segment of the uterus than the fetus\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMethods of termination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eChange termination method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eVolume of blood during termination, ml\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eProgression to GTN\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e12.1\u0026times;12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e1.0\u0026times;10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRequest for termination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eForcep curettage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes, chemotherapy 1 month after termination\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e5.0\u0026times;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e2.5\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRequest for termination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eForcep curettage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e18.5\u0026times;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHyperthyroidism, vaginal bleeding, bilateral ovarian luteinized cyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e3.5\u0026times;10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRequest for termination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eForcep curettage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e2500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes, chemotherapy 2 month after termination\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e14.0\u0026times;12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e6.1\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRequest for termination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCombination of mifepristone and misoprostol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e5.6\u0026times;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e1.4\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRequest for termination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCombination of mifepristone and misoprostol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e13.0\u0026times;10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInvasive hydatidiform mole, intrauterine fetal death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e2.2\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eIntrauterine fetal death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIntra-amniotic injection of rivanol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eChange to esarean section due to massive bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes, chemotherapy immediately after termination\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e10.1\u0026times;5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e4.1\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSingleton normal fetus with partial hydatidiform mole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRequest for termination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIntra-amniotic injection of rivanol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e16.3\u0026times;15.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHyperthyroidism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e8.8\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSingleton normal fetus with partial hydatidiform mole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRequest for termination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIntra-amniotic injection of rivanol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e2100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e10.5\u0026times;6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e1.0\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSingleton normal fetus with partial hydatidiform mole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eIntrauterine fetal death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIntra-amniotic injection of rivanol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e19.7\u0026times;16.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSevere pre-eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e8.5\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePre-eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e1200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e18.4\u0026times;16.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePre-eclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e3.3\u0026times;10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRequest for termination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e700\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e6.0\u0026times;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRespiratory failure, invasive hydatidiform mole, vaginal bleeding, bilateral ovarian luteinized cyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e2.3\u0026times;10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eInvasive hydatidiform mole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes, chemotherapy immediately after termination\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e15.2\u0026times;7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e6.8\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRequest for termination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c4\"\u003e \u003cp\u003e16.0\u0026times;11.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVaginal bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026times;\" colname=\"c6\"\u003e \u003cp\u003e1.7\u0026times;10\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTwin pregnancies combining a complete hydatidiform mole coexisting with a normal fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eVaginal bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eYes, chemotherapy 18 days after termination\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"13\"\u003eAbbreviations: hCG, human chorionic gonadotropin; GTN, gestational trophoblastic neoplasm.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA) Forceps curettage group\u003c/p\u003e \u003cp\u003e3 patients underwent curettage, with gestational ages of 11\u0026ndash;14 weeks. The maximum diameters of hydatidiform moles were 5.0-18.5 cm. The hCG levels in 2 patients were \u0026gt;\u0026thinsp;8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L. The molar tissues in 2 patients were closer to the lower segment of the uterus compared with the fetus. Massive blood loss occurred in 1 patient (2500 ml) and progression to GTN occurred in 2 patients.\u003c/p\u003e \u003cp\u003eB) Combination of mifepristone and misoprostol group\u003c/p\u003e \u003cp\u003e2 patients were administered combination of mifepristone and misoprostol to terminate pregnancy, with gestational ages of 14\u0026ndash;16 weeks. The maximum diameters of hydatidiform moles were 5.6\u0026ndash;14.0 cm. The hCG levels in 2 patients were less than 8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L. The molar tissue in 1 patient was closer to the lower segment of the uterus compared with the fetus. The 2 patients underwent curettage after the discharge of fetus and hydatidiform mole. No massive blood loss and no progression to GTN occurred.\u003c/p\u003e \u003cp\u003eC) Intra-amniotic injection of rivanol group\u003c/p\u003e \u003cp\u003e4 patients underwent intra-amniotic injection of rivanol, with gestational ages of 19\u0026ndash;26 weeks. The maximum diameters of hydatidiform moles were 10.1\u0026ndash;16.3 cm. The hCG level in 1 patient was \u0026gt;\u0026thinsp;8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L. The molar tissues in 2 patients were closer to the lower segment of the uterus compared with the fetus. Successful induction was achieved in 3 patients, and the termination method changed to cesarean section in 1 patient due to massive blood loss during the termination process. Massive blood loss occurred in 2 patients (1100 ml, 2100ml) and progression to GTN occurred in 1 patient.\u003c/p\u003e \u003cp\u003eD) Cesarean section group\u003c/p\u003e \u003cp\u003e5 patients underwent cesarean section, with gestational ages of 16\u0026ndash;18 weeks. The maximum diameters of hydatidiform moles were 6.0-19.7 cm. The hCG levels in 4 patients were \u0026gt;\u0026thinsp;8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L. The molar tissues in 5 patients were closer to the lower segment of the uterus compared with the fetus. Massive blood loss occurred in 4 patients (400ml, 400ml, 700ml, 1200ml) and progression to GTN occurred in 2 patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eMassive blood loss\u003c/h2\u003e \u003cp\u003eAmong all 14 patients, 7 patients had massive blood loss during termination of pregnancy, with an incidence of 50.0%. The comparison between patients with massive blood loss and without massive blood loss was shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Among the 7 patients with massive blood loss, the maximum diameters of hydatidiform mole were over 15 cm in 5 patients; serum hCG levels were over 8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L in 5 patients; molar tissues were closer to the lower segment of the uterus than the fetus in 7 patients; and hydatidiform mole related complications were found in 6 patients. Results of this study showed that molar tissues closer to lower segment of the uterus than the fetus (P\u0026thinsp;=\u0026thinsp;0.035) and presence of complications (P\u0026thinsp;=\u0026thinsp;0.015) were risk factors for massive blood loss during termination of pregnancy. The correlation between serum hCG level\u0026thinsp;\u0026gt;\u0026thinsp;8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L, the maximum diameter of hydatidiform mole\u0026thinsp;\u0026gt;\u0026thinsp;15cm, and the risk of massive blood loss during termination of pregnancy needed further study.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison between patients with massive blood loss and without massive blood loss.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMassive blood loss\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWithout massive blood loss\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe maximum diameter of hydatidiform mole\u0026thinsp;\u0026gt;\u0026thinsp;15cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum hCG level\u0026thinsp;\u0026gt;\u0026thinsp;8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMolar tissues closer to the lower segment of the uterus than the fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: hCG, human chorionic gonadotropin\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe incidence of massive blood loss in medication termination group (combination of mifepristone and misoprostol, and intra-amniotic injection of rivanol) was not lower than that in surgical termination group (forceps curettage and cesarean section) (P\u0026thinsp;=\u0026thinsp;0.296) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The relationship between different termination methods and risk of massive blood loss needed to be clarified in larger sample size study.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of major complications between the medication termination group and the surgical termination group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplications\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe medication termination group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThe surgical termination group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMassive blood loss\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.296\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgression to GTN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.238\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: GTN, gestational trophoblastic neoplasm.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eProgression to GTN\u003c/h2\u003e \u003cp\u003eAmong all 14 patients, progression to GTN was confirmed in 5 patients, with an incidence of 35.7%. 2 patients were diagnosed invasive hydatidiform mole based on lung compute tomography before termination of pregnancy, and 3 were diagnosed invasive hydatidiform mole within 2 months after termination. The comparison between patients with progression to GTN and without progression to GTN was shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Among the 5 patients with progression to GTN, the maximum diameters of hydatidiform mole were over 15 cm in 2 patients; serum hCG levels were over 8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L in 4 patients; molar tissues were closer to the lower segment of the uterus than the fetus in 5 patients; and hydatidiform mole related complications were found in 4 patients. The risk factors for progression to GTN after termination in the second trimester still needed to be confirmed in further researches.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison between patients with progression to GTN and without progression to GTN.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProgression to GTN\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWithout progression to GTN\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe maximum diameter of hydatidiform mole\u0026thinsp;\u0026gt;\u0026thinsp;15cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.657\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum hCG level\u0026thinsp;\u0026gt;\u0026thinsp;8 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMolar tissues closer to the lower segment of the uterus than the fetus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.126\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: hCG, human chorionic gonadotropin; GTN, gestational trophoblastic neoplasm.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn terms of the methods of termination of pregnancy (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), in the medication therapy group, including combination of mifepristone and misoprostol and intra-amniotic injection of rivanol, 1 out of 6 patients progressed to GTN (1 patient diagnosed GTN before termination of pregnancy); while in the surgical group, including forceps curettage and cesarean section, 4 out of the 8 patients progressed to GTN (1 patient diagnosed GTN before termination of pregnancy). The risk of progression to GTN was not different between the medication therapy group and the surgical group.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe 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\u0026thinsp;=\u0026thinsp;0.035), and presence of complications (P\u0026thinsp;=\u0026thinsp;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.\u003c/p\u003e \u003cp\u003eIn 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[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. 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[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. 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[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. 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[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. 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[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Some studies had shown that low serum hCG level was the best indicator to predict fetal survival rate (P\u0026thinsp;=\u0026thinsp;0.006), and serum hCG level lower than 400000 IU/L was a good candidate for continuing pregnancy and achieving fetal survival[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, termination of pregnancy seemed to be a safe option in patients with serious complications, high serum hCG levels or suspected lung metastasis.\u003c/p\u003e \u003cp\u003eLittle 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.\u003c/p\u003e \u003cp\u003eThere 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\u0026ndash;20% of patients in complete hydatidiform mole and 1.5% in partial hydatidiform mole[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The risk of progression to GTN in hydatidiform mole coexisting with a normal fetus was higher than that of single complete moles[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A multi-center study showed that the overall incidence of GTN after hydatidiform mole coexisting with a normal fetus was 46%[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Compared with patients with natural remission, patients with GTN showed higher levels of hCG (250000 IU/L vs 120000 IU/L, p\u0026thinsp;=\u0026thinsp;0.026) and higher rates of termination of pregnancy due to complications (20% vs 0%, p\u0026thinsp;=\u0026thinsp;0.006)[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. A literature review summarized 36 patients of singleton normal fetus with partial hydatidiform mole, and the incidence of GTN was 25.0%[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Compared with termination of pregnancy at less than 24 weeks of gestation, over 24 weeks of gestation was a protective factor for GTN[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], 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.\u003c/p\u003e \u003cp\u003eThere was a lack of researches on the methods of termination of pregnancy in the second trimester of hydatidiform mole coexisting with a normal fetus[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Some scholars suggested that there was controversy over the intra-amniotic injection of rivanol and intravenous injection of oxytocin in the second trimester[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], 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[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. 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[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. 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[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and Wang held similar opinion[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. 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.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eTo 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.\u003c/p\u003e \u003cp\u003eSince 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.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eDifferent methods of terminating pregnancy in the second trimester of hydatidiform mole coexisting with a normal fetus were feasible, including forceps curettage, combination of mifepristone and misoprostol, intra-amniotic injection of rivanol, and cesarean section. Different termination methods might lead to complications including massive blood loss and progression to GTN. The incidence of massive blood loss was high, and molar tissues closer to the lower uterine segment than the fetus and presence of complications were risk factors. Further researches were needed to investigate the risk factors for progression to GTN.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design: GZ, WC, PP; provision of study materials or patients: GZ, WC, LJ, XL, CL, LT, JZ, XW, YX; data analysis and interpretation: GZ, WC, PP; manuscript writing: GZ, WC; manuscript revision: PP, XL, CL, LT ;all authors have read and agreed to the final version of the paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupported by National High Level Hospital Clinical Research Funding, No. 2022-PUMCH-A-232.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article, and further inquiries can be directed to the corresponding authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of Peking Union Medical College Hospital, and\u0026nbsp;informed consent was obtained from study participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWarton EM, Dickinson JE, White SW, et al. 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J Gynecol Obstet Hum Reprod. 2022;51(1):102269.\u003c/li\u003e\n\u003cli\u003eKihara M, Usui H, Tanaka H, et al. Complicating preeclampsia as a predictor of poor survival of the fetus in complete hydatidiform mole coexistent with twin fetus. J Reprod Med. 2012;57(7-8):325-8.\u003c/li\u003e\n\u003cli\u003eSuksai M, Suwanrath C, Kor-Anantakul O, et al. Complete hydatidiform mole with co-existing fetus: Predictors of live birth. Eur J Obstet Gynecol Reprod Biol. 2017;212:1-8.\u003c/li\u003e\n\u003cli\u003eSeckl MJ, Sebire NJ, Berkowitz RS. Gestational trophoblastic disease. Lancet. 2010;376(9742):717-29.\u003c/li\u003e\n\u003cli\u003eLurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010;203(6):531-9.\u003c/li\u003e\n\u003cli\u003eNiemann I, Sunde L, Petersen LK. 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Complete hydatidiform mole presenting as a placenta accreta in a twin pregnancy with a coexisting normal fetus: case report. Case Rep Obstet Gynecol. 2012;2012:405085.\u003c/li\u003e\n\u003cli\u003eZhang RQ, Zhang JR, Li SD. Termination of a partial hydatidiform mole and coexisting fetus: A case report. World J Clin Cases. 2019;7(20):3289-95.\u003c/li\u003e\n\u003cli\u003eWang Y, Qian H, Wang J. Medical termination of a partial hydatidiform mole and coexisting fetus during the second trimester: A case report. Oncol Lett. 2015;10(6):3625-8.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hydatidiform mole coexisting with a normal fetus, termination, complication, massive blood loss, progression to gestational trophoblastic.","lastPublishedDoi":"10.21203/rs.3.rs-4625376/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4625376/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eTo explore the safety of different termination methods of hydatidiform mole coexisting with a normal fetus in the second trimester of pregnancy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis is a retrospective cohort study conducted in a referral center for difficult and critical diseases in Obstetrics and Gynecology in Beijing, China. Patients diagnosed hydatidiform mole coexisting with a normal fetus who received termination of pregnancy in the second trimester (12 weeks to 27\u003csup\u003e+6\u003c/sup\u003e weeks) were enrolled. The primary end point was the safety of different termination methods, including the volume of blood loss and progression to gestational trophoblastic neoplasm.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Different methods of terminating pregnancy in the second trimester of hydatidiform mole coexisting with a normal fetus were feasible, including forceps curettage, combination of mifepristone and misoprostol, intra-amniotic injection of rivanol, and cesarean section. 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 gestational trophoblastic neoplasm was 35.7%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eDifferent termination methods might lead to complications including massive blood loss and progression to gestational trophoblastic neoplasm. More medical measures should be taken to prevent and reduce the volume of bleeding among patients with high risk factors.\u003c/p\u003e","manuscriptTitle":"Safety of different termination methods for hydatidiform mole coexisting with a normal fetus in the second trimester","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-19 20:24:38","doi":"10.21203/rs.3.rs-4625376/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7e4042fb-37dd-44e6-a88e-e8eb23935670","owner":[],"postedDate":"July 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-06T19:08:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-19 20:24:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4625376","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4625376","identity":"rs-4625376","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}