Human Reproduction, Vol. 16, No. 6, 1274-1277,
June 2001
© 2001 European Society of Human Reproduction and Embryology
Subsequent pregnancy outcome in patients with spontaneous resolution of HCG after evacuation of hydatidiform mole: comparison between complete and partial mole
Department of Obstetrics and Gynecology, Chiba University School of Medicine, Chiba, Japan
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Abstract |
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This study compared subsequent pregnancy outcome in patients with complete and partial hydatidiform moles. Among 1052 patients with molar pregnancy (complete mole, 801; partial mole, 251) monitored at Chiba University Hospital between 1981 and 1999, 891 patients (84.7%) had spontaneous resolution of human chorionic gonadotrophin (HCG) after mole evacuation, and 161 patients (15.3%) required chemotherapy. Of the 891 patients, 438 (49.2%) had 650 subsequent pregnancies. The pregnancy outcome was not significantly different in patients with complete and partial moles, and was comparable with that in the general Japanese population. The incidence of repeat molar pregnancy in patients with complete and partial mole (1.3 and 1.5% respectively) was 5-fold higher than that of the general population, while no increased risk of persistent gestational trophoblastic tumour (GTT) associated with later molar pregnancy was observed. During HCG follow-up, 10 patients (1.1%) developed secondary high-risk GTT between 14 and 54 months after mole evacuation. The incidence of high-risk GTT in patients with and without subsequent pregnancies was 0.46% (2/438) and 1.8% (8/453) respectively (P = 0.1243). In conclusion, patients with complete and partial mole can anticipate a normal future reproductive outcome, and pregnancies after experiencing hydatidiform mole may not affect the development of high-risk GTT.
Key words: gestational trophoblastic tumour/molar pregnancy/pregnancy outcome
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Introduction |
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Both complete mole (CM) and partial mole (PM) occur predominantly in young women of reproductive age. Human chorionic gonadotrophin (HCG) is resolved spontaneously after evacuation of the mole in ~80–90% of patients (Bagshawe et al., 1986
; Matsui et al., 1996). Patients with CM and PM are usually observed by serial HCG assays until HCG regresses to undetectable concentrations. During the HCG follow-up period, patients are strongly recommended to use reliable contraception for ~6 months. However, this waiting period before undertaking further pregnancy is based on clinical experience, and there has never been a prospective investigation (Kohorn, 1999).
On completion of HCG follow-up, many patients may attempt to conceive. However, both patients and their partners commonly express fears related to future pregnancies and risk of later episodes of gestational trophoblastic tumour (GTT). Therefore, data related to subsequent pregnancies are essential for the rational counselling of patients and their partners with regard to the probability of normal pregnancy in the future (Wenzel et al., 1992).
The current study was undertaken to determine the subsequent pregnancy outcome in patients who had experienced molar pregnancy of CM and PM.
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Materials and methods |
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Between 1981 and 1999, 1052 patients with hydatidiform mole (801 with CM, 251 with PM) were monitored at the Chiba University Hospital. Complete and partial moles were diagnosed based on macroscopic findings at evacuation of the mole. Pathologically, the swelling of all chorionic villi and the absence of embryonal components were diagnosed as CM, and the mixture of normal and swollen chorionic villi and the presence of focal trophoblastic hyperplasia with or without embryonal components were diagnosed as PM. Among the 1052 patients, 891 (84.7%) had spontaneous resolution of HCG after evacuation of the mole alone, and 161 patients (15.3%) required chemotherapy to achieve remission. The patient group with spontaneous resolution of HCG was analysed in the present study. The mean (± SD) maternal age was 29.4 ± 7.0 years, and 373 patients (41.9%) had no children at the evacuation of mole. Thirteen patients (1.5%) had a history of previous molar pregnancy, while no patients required chemotherapy to achieve remission. After evacuation of the hydatidiform mole, all patients were recommended to use reliable contraception until spontaneous resolution of serum HCG titres (<1 mIU/ml) was confirmed and after at least three ovulatory cycles monitored by basal body temperature.
All patients were followed for at least 2 years, and 438 of the 891 patients (49.2%) had a total of 650 subsequent conceptions. The pregnancy outcomes were compared in patients with CM and PM. The interval to subsequent conception was calculated from the date of mole evacuation to the last menstrual period before the pregnancy.
Ten (1.1%) patients who had spontaneous resolution of HCG developed high-risk GTT based on modified Hammond's criteria (Hammond et al., 1973; Matsui et al., 2000). All patients were treated with combination chemotherapy, and eight patients were alive and well at the last follow-up examination. The latent period to GTT development in these 10 patients ranged from 14 to 54 months.
Statistical analyses were performed by Welch's t-test, analysis of variance (ANOVA) was followed by Scheffé's F-test and the 
2 test.
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Results |
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The 650 conceptions subsequent to evacuation of CM and PM resulted in 489 (75.2%) term live births, three (0.5%) stillbirths, 11 (1.7%) premature deliveries, 84 (12.9%) spontaneous abortions, 54 (8.3%) therapeutic abortions and nine (1.4%) repeat moles (Table I
). There were eight cases (1.2%) of twin pregnancies. Although there were no significant differences in the outcome of subsequent pregnancies between patients with CM and PM, the incidence of premature delivery was significantly increased in patients with PM (P = 0.0219). However, the premature deliveries included one twin pregnancy in a patient with PM. Excluding this twin case, the difference in incidence of premature delivery between patients with CM and PM did not reach statistical significance (P = 0.0741). Both major and minor congenital anomalies were detected at birth or during the nursing period in seven (1.4%) infants (meningocele, spina bifida, cleft palate, pyloric stenosis, preauricular skin-tag, syndactyly and congenital cystic adenomatoid malformation). The modes of delivery in 500 term live births and premature deliveries were vaginal in 468 (93.6%) and Caesarean section in 32 (6.4%). The mean (± SD) birth weight in 482 term live births, excluding twins, was 3289 ± 381 g. These birth weights were comparable with the standard physical growth statistics for 1998 in Japan (Ministry of Health and Welfare, 1998). The sex ratio was 254 males (52.7%) to 228 females (47.3%).
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Among the 650 conceptions, 438 subsequent first pregnancies resulted in 341 (77.9%) term live births, two (0.5%) stillbirths, eight (1.8%) premature deliveries, 52 (11.9%) spontaneous abortions, 27 (6.2%) therapeutic abortions and eight (1.8%) repeat moles (Table II
). The mean (± SD) waiting period between mole evacuation and subsequent first pregnancy was 14.4 ± 11.9 months. Pregnancies that occurred within 6 months after evacuation of the mole (n = 102) resulted in 77 (75.5%) term live births, three (3.0%) premature deliveries, 12 (11.8%) spontaneous abortions, eight (7.8%) therapeutic abortions and two (2.0%) repeat moles. These pregnancy outcomes were similar to those in patients who conceived after more than 6 months.
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The main fears expressed by patients and their partners were repeat mole and secondary development of GTT after subsequent pregnancy. Nine cases of repeat molar pregnancy (1.4%) were observed in this series (Table I
), and all of the patients had spontaneous resolution of HCG after evacuation of mole alone. The incidence of repeat molar pregnancy was ~5-fold higher than that of the general population.
During follow-up, 10 patients (1.1%) developed secondary high-risk GTT after their serum HCG had regressed spontaneously to undetectable levels (Table III). All cases of high-risk GTT were diagnosed based on modified Hammond's criteria (Hammond et al., 1973; Matsui et al., 2000), and all patients were treated with methotrexate, etoposide and actinomycin D combination chemotherapy (Matsui et al., 2000). The mean (± SD) latent period from evacuation of hydatidiform mole was 32.6 ± 12.6 months (range: 14–54 months). Two patients (Cases 9 and 10) had normal pregnancy before the occurrence of high-risk GTT. Case 1 died within 4 weeks of the initiation of treatment, and Case 9 died of chemotherapy-related toxicity; the other eight patients were alive and with no evidence of disease at the last follow-up examination. The mean (± SD) new WHO score was 8.7 ± 3.6 (Kohorn et al., 2000), while two patients (Cases 4 and 9) had scores of 
6. In Case 9, secondary GTT (WHO score 3) occurred 35 months after evacuation of the mole, and 3 months after vaginal delivery of a live birth. Both patients with new WHO score of 6 were histologically diagnosed as having choriocarcinoma. The incidence of high-risk GTT in patients with and without subsequent pregnancies was 0.46% (2/438) and 1.8% (8/453) respectively (P = 0.1243).
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Discussion |
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Hydatidiform mole has a high incidence among women in their twenties and thirties, and most patients with this condition strongly desire future pregnancy. Therefore, data related to subsequent pregnancies after hydatidiform mole are essential to counsel patients and their partners concerning potential risks of later conceptions. Many previous studies (Pastorfide and Goldstein, 1973
; Ngan et al., 1988; Berkowitz et al., 1994, 1998; Yapar et al., 1994) have concluded that patients with CM can be assured that they may anticipate a normal reproductive outcome, and that patients with PM also may expect a similar reproductive outcome.
In the current series, the rates of term live birth, stillbirth, premature delivery, spontaneous abortion and congenital anomaly in patients who had experienced molar pregnancy were similar to the rates in the general Japanese population (Ministry of Health and Welfare, 1998) and those reported in the literature. In addition, no differences in these rates were observed between complete and partial mole cases. The rate of Caesarean section was lower than that reported previously (Berkowitz et al., 1994; Kim et al., 1998).
The only significant finding was that the patients had an increased risk of recurrent molar pregnancy in subsequent conceptions (1.4%). In Chiba Prefecture, the average incidence of hydatidiform mole was 2.94 per 1000 live births. Therefore, the recurrent molar pregnancy rate was 5-fold higher than the rate of molar pregnancy of the general population (Takamizawa et al., 1987). The increased risk of recurrent molar pregnancy in the current study was compatible with the values previously reported (Sand et al., 1984; Ngan et al., 1988; Berkowitz et al., 1994, 1998; Yapar et al., 1994).
An increased risk of developing persistent GTT in subsequent repeat molar pregnancy has been reported (Federschneider et al., 1980; Bagshawe et al., 1986; Ngan et al., 1988; Berkowitz et al., 1994, 1998; Yapar et al., 1994). However, all nine patients who had repeat molar pregnancy in the current series achieved spontaneous remission by evacuation of the mole alone. Although the reason for this discrepancy is unclear, a possible explanation is that patients with repeat mole were small, and six of these moles (66.7%) were only partial in nature.
Recently, the recommended period of contraception after molar pregnancy has been shortened, but the subsequent pregnancy outcome related to the waiting period in patients who had hydatidiform mole has not been reported (Kohorn, 1999). In the current authors' hospital, patients who had spontaneous resolution of HCG after evacuation of the mole alone were strongly encouraged to use reliable contraception until spontaneous resolution of serum HCG titres (<1 mIU/ml) were confirmed, and after at least three ovulatory cycles had been monitored by basal body temperature. Approximately one-quarter of the patients conceived within 6 months of mole evacuation, and the pregnancy outcome was comparable with that of the general Japanese population. Although the current study included only small patient numbers, and was retrospective in nature, these findings suggest that it may be safe to conceive after a waiting period shorter than 6 months.
The other fear concerning future pregnancy that is expressed by both patients and their partners is that of secondary development of GTT in subsequent pregnancies. Ten patients (1.1%) with spontaneous regression of HCG developed high-risk GTT after a period of 32.6 ± 12.6 months (range: 14–54 months). Two patients had term live births before the onset of high-risk GTT. Although the genetic identities of the pregnancies responsible for high-risk GTT were unclear in these two cases (Osada et al., 1991), the incidence of high-risk GTT tended to be lower in patients who had new pregnancies before onset of high-risk GTT than in those who did not become pregnant (P = 0.1243). These results suggest that conception subsequent to evacuation of a mole may not influence the development of secondary GTT.
In conclusion, patients with complete and partial moles can anticipate a normal future reproductive outcome. Because most pregnancies that occur within 6 months from evacuation of the hydatidiform mole result in a favourable outcome, a waiting period until HCG concentrations are undetectable, and at least three ovulatory cycles are confirmed, may suffice. Repeat molar pregnancy is the only unfavourable event in subsequent pregnancy in patients with complete and partial moles, and the incidence is increased 5-fold compared with the general population. A subsequent pregnancy after hydatidiform mole may not affect the development of high-risk GTT.
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Notes |
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1 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail: hmatsui{at}ho.chiba-v.ac.jp
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Submitted on September 5, 2000; accepted on February 23, 2001.
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