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Subsequent Reproductive Experience after Treatment for Gestational Trophoblastic Disease
GYNECOLOGIC ONCOLOGY ARTICLE NO.
71, 108 –112 (1998)
GO985167
Subsequent Reproductive Experience after Treatment for Gestational Trophoblastic Disease1 Jae Hoon Kim,2 Dong Choon Park, Seog Nyeon Bae, Sung Eun Namkoong, and Seung Jo Kim Department of Obstetrics and Gynecology, Research Institute for Trophoblastic Disease, The Catholic University of Korea, Seoul, Korea Received March 6, 1998
Purpose. The purpose of this study was to evaluate reproductive performance of patients with gestational trophoblastic disease (GTD) after completion of treatment and follow-up periods. Patients and methods. Subjects comprised 115 patients who became pregnant after having been judged completely cured after a follow-up period of at least 1 year. There were 77 hydatidiformmole patients who had a natural cure and 38 gestational trophoblastic tumor patients who were cured after chemotherapy. We studied these patients with respect to parameters concerning pregnancy outcome. Results. Average age at first pregnancy was 28.0 and average number of past deliveries was 1.3. After a 1-year contraception period, the average time to the next pregnancy was 0.8 year, with 59 of 115 (51.3%) women becoming pregnant within 1 year after pregnancy was permitted and 98 women (85.2%) conceiving within 3 years. Results of the pregnancies after cure of GTD did not deviate from normal ranges in separated analyses of complete mole (CM), partial mole (PM), and gestational trophoblastic tumor. Rate of repeat mole was found to be high, occurring in 5 of 115 (4.3%) cases. Rates of antepartum and postpartum complications did not deviate from normal ranges, and there was nothing peculiar about the neonatal sex and weight. Conclusion. GTD and chemotherapy rarely affect later pregnancies; however, the rate of repeat mole is relatively high. © 1998 Academic Press
Gestational trophoblastic disease (GTD) is a disease that leads to an abnormal increase in trophoblasts, and it histologically includes hydatidiform mole (H-mole), invasive mole, gestational trophoblastic tumor (GTT), and placental trophoblastic disease [1]. It is known to occur frequently in Asia, and in Korea, it occurs in every 500 deliveries [2]. GTD responds well to chemotherapy, and is relatively easy to diagnose, follow up, and judge as cured or not, using human chorionic b-gonadotropin (b-hCG), the tumor marker. In addition, its treatment methods vary according to the confirmation of high1
This work was supported by in part by Clinical Research Funds of Korean Research Institute of Trophoblastic Disease. 2 To whom reprint requests should be addressed at Saint Vincent’s Hospital, 93 Gi Dong Paldal Gu, Suwon, Geong Gi Do, Korea. 0090-8258/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.
risk factors, enabling better treatment results compared with other malignant tumors [3]. The disease occurs mostly in women under the age of 35 [4], and therefore, it is necessary to examine the prognosis of later pregnancies, especially the possibility of recurrence of GTD and anomalies resulting from the use of anticancer medicine. In actuality, 42 to 63% percent of GTD patients fear the results of later pregnancies [5]. For these reasons, we conducted research on pregnancy after cure of GTD. PATIENTS AND METHODS Subjects comprised 115 patients who became pregnant after being judged completely cured after a follow-up period of at least 1 year among 517 GTD patients who visited the Department of Obstetrics and Gynecology, Catholic University School of Medicine, between January 1985 and December 1995. There were 77 H-mole patients who had a natural cure and 38 GTT patients who were cured after chemotherapy. We studied the following parameters by reviewing the patients’ medical records and mail surveys: term live birth, premature delivery, stillbirth delivery, spontaneous abortion, ectopic pregnancy, repeat mole, congenital anomaly, prognosis of antepartum and postpartum complications, modes of delivery, indications for Cesarean section, and distribution of neonatal sex and weight. RESULTS 1. Age and Past Deliveries Patient age ranged between 21 and 44; the average age was 28.0. The majority of patients (62) were between 26 and 30 (53.9%); 5 women (4.3%) were above the age of 36 (Table 1). Their average number of past deliveries was 1.3. There were 48 (41.7%) women who had no delivery experience and 12 (10.4%) who had four or more past deliveries (Table 2). 2. Period between GTD and the Next Pregnancy Average period between confirmation of cure after a follow-up period of 1 year and the next pregnancy was 0.8 year.
108
109
REPRODUCTIVE EXPERIENCE AFTER TREATMENT OF GTD
TABLE 1 Distribution of Age
TABLE 3 Intervals between Completion of Follow-up and First Pregnancy
Age
No. of cases
%
Years
16–20 21–25 26–30 31–35 36–40 41–45 46–
0 22 62 26 2 3 0
0.0 19.1 53.9 22.6 1.7 2.6 0
,1 1–2 2–3 3–4 4–5 5–6 6–7
Total
115
100.0
Among the total 115 women, 59 (51.3%) became pregnant within 1 year after pregnancy was permitted. A total of 88 (76.5%) women became pregnant within 2 years and 105 (91.3%) within 3 years after permission (Table 3). 3. First Pregnancy after Cure of GTD
No. of cases
%
59 29 17 5 2 2 1
51.3 25.2 14.8 4.3 1.7 1.7 0.1
115
100.0
Total
different from the average rates in general cases. There was no significant difference among the two groups. Repeat mole occurred in 2 (2.6%) and 3 (9.6%) cases, respectively, with both rates higher than 0.2%, the general occurrence rate of H-mole in Korea (Tables 5, 6).
There were 89 (77.4%) term live births, 3 (2.6%) premature deliveries, 1 (0.9%) stillbirth delivery, and 3 (2.6%) ectopic pregnancies, and the rates were not much different from the average rates in general cases. However, there were 5 (4.3%) repeat mole cases, a higher rate compared with the average occurrence rate of 0.2% in Korea. Cesarean section was done in 32 (34.4%) of 93 deliveries, a rate not higher than the 7339 (41.16%) of 17,831 deliveries that occurred at the hospitals during the same period. Congenital anomaly occurred in 3 (3.2%) cases, one each of congenital heart disease, perochirus, and accessory ear (Table 4).
5. Second Pregnancy after Cure of GTD
4. Hydatidiform-Mole and GTT
The results of the first pregnancy after cure in 65 naturally cured complete H-mole patients were 54 (83.1%) term live births, zero (0.0%) premature births, 1 (1.5%) stillbirth delivery, 6 (9.2%) spontaneous abortions, 2 (3.8%) ectopic pregnancies, and 2 (3.8%) repeat moles. In the case of partial H-mole patients, the results of their first pregnancy after cure
The results of the first pregnancy after cure in 77 naturally cured H-mole patients and 38 GTT patients who underwent chemotherapy were 64 (83.1%) and 25 (65.8%) term life births, zero (0.0%) and 3 (7.9%) cases deliveries, 1 (0.87%) and zero (0.0%) stillbirth deliveries, 8 (10.3%) and 6 (15.8%) spontaneous abortions, and 2 (2.6%) and 1 (2.6%) ectopic pregnancies, respectively, with rates in both groups not much
Seven women among the naturally cured H-mole patients had more than one pregnancy after being cured; among them, 5 (71.4%) had term live births, and 2 (28.6%) had spontaneous abortions. Among the GTT patients who were cured after chemotherapy, 12 women had more than one pregnancy after the cure; 8 (66.7%) had term live births, 1 (8.3%) had a premature birth, and 3 (25.0%) had spontaneous abortions (Tables 7, 8). 6. Complete and Partial Mole
TABLE 4 Outcomes of First Pregnancies in Women with GTD
TABLE 2 Distribution of Parity Parity 0 1 2,3 4,5 6,7 Total
No. of cases
%
48 29 26 9 3
41.7 25.2 22.6 7.8 2.6
115
100.0
Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly Cesarean section
89 3 1 14 3 5 3 32
77.4 2.6 0.9 12.2 2.6 4.3
115
100.0
Total
No./deliveries (%)
3/93 (3.2) 32/93 (34.4)
110
KIM ET AL.
TABLE 5 Outcomes of First Pregnancies in Women with HM Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly Cesarean section
64 0 1 8 2 2 2 14
83.1 0.0 1.3 10.3 2.6 2.6
Total
77
100.0
TABLE 7 Outcomes of Second Pregnancies in Women with HM
No./deliveries (%)
2/65 (3.1) 14/65 (21.6)
Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly
5 0 0 2 0 0 0
71.4 0.0 1.3 6 0.0 0.0 0.0
Total
7
100.0
were 10 (80%) full-term deliveries and 2 (20%) spontaneous abortions (Tables 9, 10).
(9.4%) of fetal distress, 2 cases (6.3%) of high-risk pregnancy, 2 cases (6.3%) of breech, and 2 cases (6.3%) of placenta previa (Table 12).
7. Antepartum and Postpartum Complications
9. Neonatal Sex and Weight
The most common antepartum complication was premature rupture of membranes, with 10 (10.8%) cases occurring. In addition, there were 3 (3.2%) threatened abortions, 5 (5.4%) cases of preterm labor, 2 (2.2%) cases of breech, 2 (2.2%) cases of placenta previa, 9 (9.7%) cases of pregnancy-induced hypertension, and 5 (5.4%) cases of placenta accreta. Concerning postpartum complications, there were 13 (14.0%) cases of anemia, 4 (4.3%) cases of third- and fourthdegree lacerations, 3 (3.2%) cases of postpartum hemorrhage, and one (1.1%) case each of thrombocytopenia, pulmonary edema, sepsis, and disseminated intravascular coagulation (Table 11).
In terms of sex of the infants, 49 (52.7%) were male and 44 (47.3%) were female. Their average weight was 3.29 kg, with the majority of 41 infants (44.1%) falling between 3.0 and 3.5 kg. A total of 91 infants (97.8%) had a normal weight between 2.5 and 4.0 kg (Table 13).
8. Mode of Delivery and Indications for Cesarean Section There were 61 cases (65.6%) vaginal deliveries and 32 (34.4%) Cesarean sections. Concerning the indications for Cesarean section, there were 6 cases (18.8%) in which Cesarean section was repeated, 11 cases (34.4%) of cephalopelvic disproportion, 9 cases (15.6%) of pelvic contracture, 3 cases TABLE 6 Outcomes of First Pregnancies in Women with GTT Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly Cesarean section
25 3 0 6 1 3 1 18
65.8 7.9 0.0 15.8 2.6 9.6
Total
38
100.0
DISCUSSION In general, gestational trophoblastic disease has a high incidence rate among women in their twenties and thirties, during which period they can conceive children. Because chemotherapy, and not surgery such as hysterectomy, is the main treatment method for the disease, most patients still have a uterus after treatment is completed successfully. As a result, most patients with GTD become pregnant again after being cured; for this reason, a study of the later pregnancies is essential. In Korea, especially, GTD occurs relatively often, in 1 of 500 deliveries, and therefore, information on pregnancy after cure of GTD, as well as its diagnosis, treatment, and follow-up, is extremely important. In a usual pregnancy, the first menstruation starts two to three TABLE 8 Outcomes of Second Pregnancies in Women with GTT
No./deliveries (%)
1/25 (4.0) 18/25 (72.0)
Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly
8 1 0 3 0 0 0
66.7 8.3 0.0 25.0 0.0 0.0 0.0
12
100.0
Total
111
REPRODUCTIVE EXPERIENCE AFTER TREATMENT OF GTD
TABLE 9 Outcomes of First Pregnancies in Women with CM Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly Cesarean section
54 0 1 6 2 2 2 10
83.1 0.0 1.5 9.2 3.8 3.8
Total
65
100.0
TABLE 11 Antepartum and Postpartum Complications
No./deliveries (%)
Diagnosis Antepartum Threatened abortion Preterm labor PROMa Breech Placenta previa Placenta acreta PIHb Postpartum Anemia Thrombocytopenia Postpartum hemorrhage Third- and fourth-degree laceration Pulmonary edema Sepsis DICc
2/55 (3.6) 10/55 (18.2)
months after miscarriage, and during the menstrual period, 83% of women ovulate. However, in the case of GTD patients, the time between cure and the next pregnancy is longer than in the case of miscarriage in a normal pregnancy, because it takes comparatively longer for the normalization of b-hCG, which can affect ovulation, and also because the patients need to use contraception during the 1-year follow-up period [6]. In this research, the average period until the next pregnancy was 0.8 year, excluding the 1-year contraceptive period, with 70.4% becoming pregnant within 1 year and 85.2% within 3 years. These rates were similar to the results of Song et al., who reported pregnancy rates of 70.4% within 1 year and 73.2% within 3 years [10]. As reported in past studies on H-mole [5, 7], this study showed that the rates of term live birth, premature delivery, stillbirth delivery, spontaneous abortion, ectopic pregnancy, and congenital anomaly in former GTD patients are similar to the overall average rates, and there is no difference between complete and partial H-moles [5]. Also, no difference was found in the second pregnancy after cure, and therefore, Hmole has been confirmed not to affect later pregnancies. In GTT patients who receive chemotherapy, there exists a possibility that the anticancer medicine may accumulate in the body and affect conceivability or generation of the fetus, and thus, the results of pregnancy after treatment are very contro-
Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Congenital anomaly Cesarean section
10 0 0 2 0 0 4
80 0 0 20 0
Total
12
100.0
3 5 10 2 2 5 9
3.2 5.4 10.8 2.2 2.2 5.4 9.7
13 1 3 4 1 1 1
14.0 1.1 3.2 4.3 1.1 1.1 1.1
Premature rupture of membranes. Pregnancy-induced hypertension. c Disseminated intravascular coagulation. b
versial. Researchers on Western patients [5, 7–9] and those on Asian patients [10, 11], reported that chemotherapy does not influence later pregnancies. There are, however, discrepancies among reports on repeat mole. According to some reports, the rate of repeat mole did not increase in former GTD patients [12, 13]; nevertheless, others have reported that the rate increases to 1% [5, 7]. In our research, repeat mole occurred in 5 (4.4%) of 115 cases. Among GTT patients who received chemotherapy, the rate was even higher, with 3 (9.6%) of 38, and among those 3 cases, chemotherapy was necessary in 2. This outcome was similar to the previous report which suggested that repeat mole tends to progress into persistent trophoblastic tumor [5]. TABLE 12 Mode of Delivery and Indications for Cesarean Section Indication
No. of cases
%
Repeat CPD1 Pelvic contracture Fetal distress High riskb Breech Placenta previa
61 32 6 11 9 3 2 2 2
65.6 34.4 18.8 34.4 15.6 9.4 6.3 6.3 6.3
93
100.0
Vaginal delivery Cesarean section
No./deliveries (%)
4/10 (40.0)
%
a
Mode of delivery
TABLE 10 Outcomes of First Pregnancies in Women with PM
No. of cases
Total a b
Cephalopelvic disproportion. Elderly prim.
112
KIM ET AL.
TABLE 13 Neonatal Sex and Weight
Sex Male Female Weight (kg) ,2.0 2.0–2.5 2.5–3.0 3.0–3.5 3.5–4.0 4.0, Total
REFERENCES
No. of cases
%
49 44
52.7 47.3
1 2 22 41 18 9
1.1 2.2 23.7 44.1 19.4 9.8
93
100.0
With respect to the results of pregnancy in five former repeat mole patients, there were two full-term deliveries, one spontaneous abortion, and one H-mole, which is a higher rate than in normal pregnancies, and these results were similar to those of others [13, 14]. Rates related to antepartum and postpartum complications and neonatal sex and weight were similar to those in normal pregnancies, as reported [10]. This research shows that the results of pregnancy after cure of GTD are not different from those in normal pregnancies. In addition, we confirmed that the anticancer medicine used to treat GTT patients does not have harmful effects on later pregnancies. However, we found that the rate of recurrence of GTD after cure was higher than the natural occurrence rate, and the rate of abnormal pregnancy increased after GTD recurred. For these reasons, a further in-depth study of trophoblastic disease is highly suggested.
1. Newland ES, Bagshawe KD, Begent RHJ, et al.: Development in chemotherapy for median and high risk patient with gestational trophoblastic tumors. Br J Obstet Gynecol 93:63– 69, 1986 2. National Federation of Medical Insurance: Medical Statistical Year Book, Seoul, Korea, 1991–1995 3. Li MD, Hetz R, Spencer DB: Effect of methotrexate upon choriocarcinoma and chorioadenoma. Proc Soc Exp Biol Med 193:361– 1956 4. Kim JH, Kim KS, BAEK IS, et al.: A clinical study on gestational trophoblastic disease. Kor J Obstet Gynecol 38:1510 –1517, 1995 5. Berkowitz RS, Bernstein MR, Laborde O, et al.: Subsequent pregnancy experience in patients with gestational trophoblastic disease. J Reprod Med 39:228 –232, 1994 6. Ho PC, Wong LS, Ma HK: Return of ovulation after evacuation of hydatidiform moles. Am J Obstet Gynecol 163:638 – 642, 1985 7. Goldstein DP, Berkowitz RS, Bernstein MR: Reproductive performance after molar pregnancy and gestational trophoblastic tumors. Clinical Obstet Gynecol 27:221–227, 1984 8. Van Thiel DH, Ross GT, Lipsett MB: Pregnancies after chemotherapy of trophoblastic neoplasms. Science 169:1326 –1327, 1970 9. Rustin GJS, Booth M, Dent J: Pregnancies after cytotoxic chemotherapy for gestational trophoblastic tumors. Br Med J 288:103–106, 1984 10. Song HZ, Wu PC, Wang YE, et al.: Pregnancy outcomes after successful chemotherapy for choriocarcinoma and invasive mole: Long term followup. Am J Obstet Gynecol 158:538 –545, 1988 11. Ngan HYS, Wong LC, Ma HK: Reproductive performance of patients with gestational trophoblastic disease in Hong Kong. Acta Obstet Gynecol Scand 67:11–14, 1988 12. Lurain JR, Sand PK, Carson SA, et al.: Pregnancy outcome subsequent to conservative hydatidiform moles. Am J Obstet Gynecol 142:1060 –1061, 1982 13. Sand PK, Lurain JR, Brewer JI: Repeat gestational trophoblastic disease. Obstet Gynecol 63:140 –144, 1984 14. Rice LW, Lage JM, Berkowitz RS, et al.: Repetitive complete and partial hydatidiform mole. Obstet Gynecol 74:217–219, 1989
71, 108 –112 (1998)
GO985167
Subsequent Reproductive Experience after Treatment for Gestational Trophoblastic Disease1 Jae Hoon Kim,2 Dong Choon Park, Seog Nyeon Bae, Sung Eun Namkoong, and Seung Jo Kim Department of Obstetrics and Gynecology, Research Institute for Trophoblastic Disease, The Catholic University of Korea, Seoul, Korea Received March 6, 1998
Purpose. The purpose of this study was to evaluate reproductive performance of patients with gestational trophoblastic disease (GTD) after completion of treatment and follow-up periods. Patients and methods. Subjects comprised 115 patients who became pregnant after having been judged completely cured after a follow-up period of at least 1 year. There were 77 hydatidiformmole patients who had a natural cure and 38 gestational trophoblastic tumor patients who were cured after chemotherapy. We studied these patients with respect to parameters concerning pregnancy outcome. Results. Average age at first pregnancy was 28.0 and average number of past deliveries was 1.3. After a 1-year contraception period, the average time to the next pregnancy was 0.8 year, with 59 of 115 (51.3%) women becoming pregnant within 1 year after pregnancy was permitted and 98 women (85.2%) conceiving within 3 years. Results of the pregnancies after cure of GTD did not deviate from normal ranges in separated analyses of complete mole (CM), partial mole (PM), and gestational trophoblastic tumor. Rate of repeat mole was found to be high, occurring in 5 of 115 (4.3%) cases. Rates of antepartum and postpartum complications did not deviate from normal ranges, and there was nothing peculiar about the neonatal sex and weight. Conclusion. GTD and chemotherapy rarely affect later pregnancies; however, the rate of repeat mole is relatively high. © 1998 Academic Press
Gestational trophoblastic disease (GTD) is a disease that leads to an abnormal increase in trophoblasts, and it histologically includes hydatidiform mole (H-mole), invasive mole, gestational trophoblastic tumor (GTT), and placental trophoblastic disease [1]. It is known to occur frequently in Asia, and in Korea, it occurs in every 500 deliveries [2]. GTD responds well to chemotherapy, and is relatively easy to diagnose, follow up, and judge as cured or not, using human chorionic b-gonadotropin (b-hCG), the tumor marker. In addition, its treatment methods vary according to the confirmation of high1
This work was supported by in part by Clinical Research Funds of Korean Research Institute of Trophoblastic Disease. 2 To whom reprint requests should be addressed at Saint Vincent’s Hospital, 93 Gi Dong Paldal Gu, Suwon, Geong Gi Do, Korea. 0090-8258/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.
risk factors, enabling better treatment results compared with other malignant tumors [3]. The disease occurs mostly in women under the age of 35 [4], and therefore, it is necessary to examine the prognosis of later pregnancies, especially the possibility of recurrence of GTD and anomalies resulting from the use of anticancer medicine. In actuality, 42 to 63% percent of GTD patients fear the results of later pregnancies [5]. For these reasons, we conducted research on pregnancy after cure of GTD. PATIENTS AND METHODS Subjects comprised 115 patients who became pregnant after being judged completely cured after a follow-up period of at least 1 year among 517 GTD patients who visited the Department of Obstetrics and Gynecology, Catholic University School of Medicine, between January 1985 and December 1995. There were 77 H-mole patients who had a natural cure and 38 GTT patients who were cured after chemotherapy. We studied the following parameters by reviewing the patients’ medical records and mail surveys: term live birth, premature delivery, stillbirth delivery, spontaneous abortion, ectopic pregnancy, repeat mole, congenital anomaly, prognosis of antepartum and postpartum complications, modes of delivery, indications for Cesarean section, and distribution of neonatal sex and weight. RESULTS 1. Age and Past Deliveries Patient age ranged between 21 and 44; the average age was 28.0. The majority of patients (62) were between 26 and 30 (53.9%); 5 women (4.3%) were above the age of 36 (Table 1). Their average number of past deliveries was 1.3. There were 48 (41.7%) women who had no delivery experience and 12 (10.4%) who had four or more past deliveries (Table 2). 2. Period between GTD and the Next Pregnancy Average period between confirmation of cure after a follow-up period of 1 year and the next pregnancy was 0.8 year.
108
109
REPRODUCTIVE EXPERIENCE AFTER TREATMENT OF GTD
TABLE 1 Distribution of Age
TABLE 3 Intervals between Completion of Follow-up and First Pregnancy
Age
No. of cases
%
Years
16–20 21–25 26–30 31–35 36–40 41–45 46–
0 22 62 26 2 3 0
0.0 19.1 53.9 22.6 1.7 2.6 0
,1 1–2 2–3 3–4 4–5 5–6 6–7
Total
115
100.0
Among the total 115 women, 59 (51.3%) became pregnant within 1 year after pregnancy was permitted. A total of 88 (76.5%) women became pregnant within 2 years and 105 (91.3%) within 3 years after permission (Table 3). 3. First Pregnancy after Cure of GTD
No. of cases
%
59 29 17 5 2 2 1
51.3 25.2 14.8 4.3 1.7 1.7 0.1
115
100.0
Total
different from the average rates in general cases. There was no significant difference among the two groups. Repeat mole occurred in 2 (2.6%) and 3 (9.6%) cases, respectively, with both rates higher than 0.2%, the general occurrence rate of H-mole in Korea (Tables 5, 6).
There were 89 (77.4%) term live births, 3 (2.6%) premature deliveries, 1 (0.9%) stillbirth delivery, and 3 (2.6%) ectopic pregnancies, and the rates were not much different from the average rates in general cases. However, there were 5 (4.3%) repeat mole cases, a higher rate compared with the average occurrence rate of 0.2% in Korea. Cesarean section was done in 32 (34.4%) of 93 deliveries, a rate not higher than the 7339 (41.16%) of 17,831 deliveries that occurred at the hospitals during the same period. Congenital anomaly occurred in 3 (3.2%) cases, one each of congenital heart disease, perochirus, and accessory ear (Table 4).
5. Second Pregnancy after Cure of GTD
4. Hydatidiform-Mole and GTT
The results of the first pregnancy after cure in 65 naturally cured complete H-mole patients were 54 (83.1%) term live births, zero (0.0%) premature births, 1 (1.5%) stillbirth delivery, 6 (9.2%) spontaneous abortions, 2 (3.8%) ectopic pregnancies, and 2 (3.8%) repeat moles. In the case of partial H-mole patients, the results of their first pregnancy after cure
The results of the first pregnancy after cure in 77 naturally cured H-mole patients and 38 GTT patients who underwent chemotherapy were 64 (83.1%) and 25 (65.8%) term life births, zero (0.0%) and 3 (7.9%) cases deliveries, 1 (0.87%) and zero (0.0%) stillbirth deliveries, 8 (10.3%) and 6 (15.8%) spontaneous abortions, and 2 (2.6%) and 1 (2.6%) ectopic pregnancies, respectively, with rates in both groups not much
Seven women among the naturally cured H-mole patients had more than one pregnancy after being cured; among them, 5 (71.4%) had term live births, and 2 (28.6%) had spontaneous abortions. Among the GTT patients who were cured after chemotherapy, 12 women had more than one pregnancy after the cure; 8 (66.7%) had term live births, 1 (8.3%) had a premature birth, and 3 (25.0%) had spontaneous abortions (Tables 7, 8). 6. Complete and Partial Mole
TABLE 4 Outcomes of First Pregnancies in Women with GTD
TABLE 2 Distribution of Parity Parity 0 1 2,3 4,5 6,7 Total
No. of cases
%
48 29 26 9 3
41.7 25.2 22.6 7.8 2.6
115
100.0
Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly Cesarean section
89 3 1 14 3 5 3 32
77.4 2.6 0.9 12.2 2.6 4.3
115
100.0
Total
No./deliveries (%)
3/93 (3.2) 32/93 (34.4)
110
KIM ET AL.
TABLE 5 Outcomes of First Pregnancies in Women with HM Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly Cesarean section
64 0 1 8 2 2 2 14
83.1 0.0 1.3 10.3 2.6 2.6
Total
77
100.0
TABLE 7 Outcomes of Second Pregnancies in Women with HM
No./deliveries (%)
2/65 (3.1) 14/65 (21.6)
Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly
5 0 0 2 0 0 0
71.4 0.0 1.3 6 0.0 0.0 0.0
Total
7
100.0
were 10 (80%) full-term deliveries and 2 (20%) spontaneous abortions (Tables 9, 10).
(9.4%) of fetal distress, 2 cases (6.3%) of high-risk pregnancy, 2 cases (6.3%) of breech, and 2 cases (6.3%) of placenta previa (Table 12).
7. Antepartum and Postpartum Complications
9. Neonatal Sex and Weight
The most common antepartum complication was premature rupture of membranes, with 10 (10.8%) cases occurring. In addition, there were 3 (3.2%) threatened abortions, 5 (5.4%) cases of preterm labor, 2 (2.2%) cases of breech, 2 (2.2%) cases of placenta previa, 9 (9.7%) cases of pregnancy-induced hypertension, and 5 (5.4%) cases of placenta accreta. Concerning postpartum complications, there were 13 (14.0%) cases of anemia, 4 (4.3%) cases of third- and fourthdegree lacerations, 3 (3.2%) cases of postpartum hemorrhage, and one (1.1%) case each of thrombocytopenia, pulmonary edema, sepsis, and disseminated intravascular coagulation (Table 11).
In terms of sex of the infants, 49 (52.7%) were male and 44 (47.3%) were female. Their average weight was 3.29 kg, with the majority of 41 infants (44.1%) falling between 3.0 and 3.5 kg. A total of 91 infants (97.8%) had a normal weight between 2.5 and 4.0 kg (Table 13).
8. Mode of Delivery and Indications for Cesarean Section There were 61 cases (65.6%) vaginal deliveries and 32 (34.4%) Cesarean sections. Concerning the indications for Cesarean section, there were 6 cases (18.8%) in which Cesarean section was repeated, 11 cases (34.4%) of cephalopelvic disproportion, 9 cases (15.6%) of pelvic contracture, 3 cases TABLE 6 Outcomes of First Pregnancies in Women with GTT Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly Cesarean section
25 3 0 6 1 3 1 18
65.8 7.9 0.0 15.8 2.6 9.6
Total
38
100.0
DISCUSSION In general, gestational trophoblastic disease has a high incidence rate among women in their twenties and thirties, during which period they can conceive children. Because chemotherapy, and not surgery such as hysterectomy, is the main treatment method for the disease, most patients still have a uterus after treatment is completed successfully. As a result, most patients with GTD become pregnant again after being cured; for this reason, a study of the later pregnancies is essential. In Korea, especially, GTD occurs relatively often, in 1 of 500 deliveries, and therefore, information on pregnancy after cure of GTD, as well as its diagnosis, treatment, and follow-up, is extremely important. In a usual pregnancy, the first menstruation starts two to three TABLE 8 Outcomes of Second Pregnancies in Women with GTT
No./deliveries (%)
1/25 (4.0) 18/25 (72.0)
Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly
8 1 0 3 0 0 0
66.7 8.3 0.0 25.0 0.0 0.0 0.0
12
100.0
Total
111
REPRODUCTIVE EXPERIENCE AFTER TREATMENT OF GTD
TABLE 9 Outcomes of First Pregnancies in Women with CM Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Repeat mole Congenital anomaly Cesarean section
54 0 1 6 2 2 2 10
83.1 0.0 1.5 9.2 3.8 3.8
Total
65
100.0
TABLE 11 Antepartum and Postpartum Complications
No./deliveries (%)
Diagnosis Antepartum Threatened abortion Preterm labor PROMa Breech Placenta previa Placenta acreta PIHb Postpartum Anemia Thrombocytopenia Postpartum hemorrhage Third- and fourth-degree laceration Pulmonary edema Sepsis DICc
2/55 (3.6) 10/55 (18.2)
months after miscarriage, and during the menstrual period, 83% of women ovulate. However, in the case of GTD patients, the time between cure and the next pregnancy is longer than in the case of miscarriage in a normal pregnancy, because it takes comparatively longer for the normalization of b-hCG, which can affect ovulation, and also because the patients need to use contraception during the 1-year follow-up period [6]. In this research, the average period until the next pregnancy was 0.8 year, excluding the 1-year contraceptive period, with 70.4% becoming pregnant within 1 year and 85.2% within 3 years. These rates were similar to the results of Song et al., who reported pregnancy rates of 70.4% within 1 year and 73.2% within 3 years [10]. As reported in past studies on H-mole [5, 7], this study showed that the rates of term live birth, premature delivery, stillbirth delivery, spontaneous abortion, ectopic pregnancy, and congenital anomaly in former GTD patients are similar to the overall average rates, and there is no difference between complete and partial H-moles [5]. Also, no difference was found in the second pregnancy after cure, and therefore, Hmole has been confirmed not to affect later pregnancies. In GTT patients who receive chemotherapy, there exists a possibility that the anticancer medicine may accumulate in the body and affect conceivability or generation of the fetus, and thus, the results of pregnancy after treatment are very contro-
Outcome
No. of cases
%
Term live birth Premature delivery Stillbirth delivery Spontaneous abortion Ectopic pregnancy Congenital anomaly Cesarean section
10 0 0 2 0 0 4
80 0 0 20 0
Total
12
100.0
3 5 10 2 2 5 9
3.2 5.4 10.8 2.2 2.2 5.4 9.7
13 1 3 4 1 1 1
14.0 1.1 3.2 4.3 1.1 1.1 1.1
Premature rupture of membranes. Pregnancy-induced hypertension. c Disseminated intravascular coagulation. b
versial. Researchers on Western patients [5, 7–9] and those on Asian patients [10, 11], reported that chemotherapy does not influence later pregnancies. There are, however, discrepancies among reports on repeat mole. According to some reports, the rate of repeat mole did not increase in former GTD patients [12, 13]; nevertheless, others have reported that the rate increases to 1% [5, 7]. In our research, repeat mole occurred in 5 (4.4%) of 115 cases. Among GTT patients who received chemotherapy, the rate was even higher, with 3 (9.6%) of 38, and among those 3 cases, chemotherapy was necessary in 2. This outcome was similar to the previous report which suggested that repeat mole tends to progress into persistent trophoblastic tumor [5]. TABLE 12 Mode of Delivery and Indications for Cesarean Section Indication
No. of cases
%
Repeat CPD1 Pelvic contracture Fetal distress High riskb Breech Placenta previa
61 32 6 11 9 3 2 2 2
65.6 34.4 18.8 34.4 15.6 9.4 6.3 6.3 6.3
93
100.0
Vaginal delivery Cesarean section
No./deliveries (%)
4/10 (40.0)
%
a
Mode of delivery
TABLE 10 Outcomes of First Pregnancies in Women with PM
No. of cases
Total a b
Cephalopelvic disproportion. Elderly prim.
112
KIM ET AL.
TABLE 13 Neonatal Sex and Weight
Sex Male Female Weight (kg) ,2.0 2.0–2.5 2.5–3.0 3.0–3.5 3.5–4.0 4.0, Total
REFERENCES
No. of cases
%
49 44
52.7 47.3
1 2 22 41 18 9
1.1 2.2 23.7 44.1 19.4 9.8
93
100.0
With respect to the results of pregnancy in five former repeat mole patients, there were two full-term deliveries, one spontaneous abortion, and one H-mole, which is a higher rate than in normal pregnancies, and these results were similar to those of others [13, 14]. Rates related to antepartum and postpartum complications and neonatal sex and weight were similar to those in normal pregnancies, as reported [10]. This research shows that the results of pregnancy after cure of GTD are not different from those in normal pregnancies. In addition, we confirmed that the anticancer medicine used to treat GTT patients does not have harmful effects on later pregnancies. However, we found that the rate of recurrence of GTD after cure was higher than the natural occurrence rate, and the rate of abnormal pregnancy increased after GTD recurred. For these reasons, a further in-depth study of trophoblastic disease is highly suggested.
1. Newland ES, Bagshawe KD, Begent RHJ, et al.: Development in chemotherapy for median and high risk patient with gestational trophoblastic tumors. Br J Obstet Gynecol 93:63– 69, 1986 2. National Federation of Medical Insurance: Medical Statistical Year Book, Seoul, Korea, 1991–1995 3. Li MD, Hetz R, Spencer DB: Effect of methotrexate upon choriocarcinoma and chorioadenoma. Proc Soc Exp Biol Med 193:361– 1956 4. Kim JH, Kim KS, BAEK IS, et al.: A clinical study on gestational trophoblastic disease. Kor J Obstet Gynecol 38:1510 –1517, 1995 5. Berkowitz RS, Bernstein MR, Laborde O, et al.: Subsequent pregnancy experience in patients with gestational trophoblastic disease. J Reprod Med 39:228 –232, 1994 6. Ho PC, Wong LS, Ma HK: Return of ovulation after evacuation of hydatidiform moles. Am J Obstet Gynecol 163:638 – 642, 1985 7. Goldstein DP, Berkowitz RS, Bernstein MR: Reproductive performance after molar pregnancy and gestational trophoblastic tumors. Clinical Obstet Gynecol 27:221–227, 1984 8. Van Thiel DH, Ross GT, Lipsett MB: Pregnancies after chemotherapy of trophoblastic neoplasms. Science 169:1326 –1327, 1970 9. Rustin GJS, Booth M, Dent J: Pregnancies after cytotoxic chemotherapy for gestational trophoblastic tumors. Br Med J 288:103–106, 1984 10. Song HZ, Wu PC, Wang YE, et al.: Pregnancy outcomes after successful chemotherapy for choriocarcinoma and invasive mole: Long term followup. Am J Obstet Gynecol 158:538 –545, 1988 11. Ngan HYS, Wong LC, Ma HK: Reproductive performance of patients with gestational trophoblastic disease in Hong Kong. Acta Obstet Gynecol Scand 67:11–14, 1988 12. Lurain JR, Sand PK, Carson SA, et al.: Pregnancy outcome subsequent to conservative hydatidiform moles. Am J Obstet Gynecol 142:1060 –1061, 1982 13. Sand PK, Lurain JR, Brewer JI: Repeat gestational trophoblastic disease. Obstet Gynecol 63:140 –144, 1984 14. Rice LW, Lage JM, Berkowitz RS, et al.: Repetitive complete and partial hydatidiform mole. Obstet Gynecol 74:217–219, 1989