1 Department of Obstetrics and Gynecology, Chiba University School of Medicine, Inohana 181, Chuo-ku, Chiba 260-8670, 2 Department of Perinato-Gynecology, Kagawa Medical University, Kagawa 761-0701, 3 Department of Reproductive Physiology and Endocrinology, Medical Institute of Bioregulation Kyushu University, Oita 874-0000 and 4 Department of Obstetrics and Gynecology, Nagoya University School of Medicine,Nagoya 466-0065, Japan
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Abstract |
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Key words: coexistent fetus/hydatidiform mole/persistent trophoblastic disease/twin pregnancy
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Introduction |
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Several case reports and reviews describe the diagnosis of HMTF by morphological criteria, DNA polyploidy or karyotype analyses (Jones et al., 1975; Block and Merrill, 1982; Thomas et al., 1987
; Lage et al., 1992
; Steller et al., 1994
; Fishman et al., 1998
). In these reports, the risk of developing maternal complications, such as pre-eclampsia and persistent trophoblastic tumour (PTT), seems to be higher in cases of HMTF than in cases of single complete mole. However, since complete cytogenetic information on both the mole and the fetus is available in only a small number of cases, it is difficult to distinguish androgenetic complete hydatidiform mole coexistent with twin live fetus (CHMTF) from triploid partial moles, especially at the early stages of gestation (Ohama et al., 1985
; Miller et al., 1993
). Moreover, it is uncertain whether management of this rare pregnancy has a greater risk of developing severe maternal complications than immediate termination.
We have reported that the incidence of PTT seems to be high in patients with CHMTF, although the number of cases was small (Matsui et al., 1999).
In this report, we survey patients with HMTF in Japan and describe the prenatal and postpartum management of this rare gestational condition.
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Materials and methods |
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Statistical analyses were performed by Welch's t-test, analysis of variance followed by Scheffe's F-test, and the 2 test.
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Results |
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Seventeen patients delivered at 34.8 ± 3.5 weeks gestation (ranged between 29 and 40 weeks). The mean (±SD) birth weight was 2059 ± 557 g (range 12803019 g). One neonate was stillborn and 16 were alive and well, with no gross anomalies.
The mean (±SD) maternal age of 72 patients with HMTF was 29.2 ± 5.0 years. The karyotypes of 27 fetuses were analysed during pregnancy or postpartum, and 25 had normal diploid karyotype while the remaining two were triploidy and trisomy. Ovulation induction had been performed in 16 patients (22.2%). Maternal complications, such as pre-eclampsia and massive bleeding, were observed in 14 patients (19.4%). PTT developed in 22 patients (30.6%).
CHMTF cases
Of the 72 cases of HMTF, 18 moles were confirmed to be of androgenetic origin by restriction fragment length polymorphism or DNA fingerprinting after delivery or termination of pregnancy (Table II). Zygosity was also examined in 12 molar parts. There were 10 homozygous androgenetic moles and two heterozygous androgenetic moles. Seven of these cases have been reported elsewhere (Harada et al., 1997
; Ishii et al., 1998
). The fetal karyotype was analysed in 14 cases and all were normal. In this group, the mean (±SD) maternal age at delivery or termination of pregnancy was 29.0 ± 4.7 years, and the gestational age was 20.0 ± 9.0 weeks. Pregnancy was terminated before the 15th gestational week in three patients. Thirteen patients intended to continue the pregnancy, but pregnancy was terminated in 10 patients because of deterioration of maternal complications or intrauterine fetal death. The overall rate of PTT in patients with these CHMTF was 50%. Lung metastases were found in six cases (cases 5, 6, 11, 14, 15 and 17). All nine patients achieved primary remission with chemotherapy alone.
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Discussion |
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The problems in the management of HMTF involve the risks of fetal abnormality, malignant trophoblastic change, and severe maternal complications. Since complete cytogenetic information on both the mole and the fetus is available only in a small number of reports, an optimal management protocol is controversial (Vejerslev, 1991; Steller et al., 1994
; Garbin et al., 1995
; Bristow et al., 1996
).
An association of fetal abnormalities with triploid partial mole pregnancy has been reported (Beischer, 1961; Block et al., 1982; Vejerslev, 1991
). Triploid fetuses tend to die before the end of the first trimester and surviving fetuses after midpregnancy are rarely encountered (Jauniaux et al., 1997
). In our patient population, there were no gross anomalies in 17 fetuses that survived to the third trimester. The karyotype of 27 fetuses was analysed during pregnancy or postpartum, and 25 were demonstrated to have normal diploid karyotype, while the remaining two fetuses were triploidy and trisomy. In cases of diploid fetus, dizygotic twin pregnancy with a complete mole is the most probable mechanism. However, the inclusion of triploid partial mole cannot be ruled out if the diagnosis is based only on ultrasound and postpartum morphological findings (Miller et al., 1993
).
Immediate termination has been recommended (Jones and Laursen, 1975; Block and Merrill, 1982) after the diagnosis of HMTF because of the risks of developing PTT and maternal medical complications. In contrast, other authors (Vejerslev, 1991
; Garbin et al., 1995
; Bristow et al., 1996
) suggested that in the absence of fetal anomaly or pre-eclampsia, the pregnancy can be allowed to continue irrespective of the development of PTT. However, cytogenetic information on both the mole and the fetus seems to be insufficient to decide whether to continue or to terminate the pregnancy (Fisher et al., 1982
; Ohama et al., 1985
; Ohmichi et al., 1986
; Vejerslev et al., 1986
; Azuma et al., 1992
; Miller et al., 1993
; Soysal et al., 1996
; Hurteau et al., 1997
). In our previous report of a limited series (Matsui et al., 1999
), the potential of malignancy in patients with CHMTF was significantly higher than that of single complete mole, while advanced gestational age was not an independent risk factor for the development of PTT.
PTT rates in simple complete mole were reported to be 12.5% (141/1130) in a previous study at our university (Matsui et al., 1999). In the present patient population, the risk of developing PTT was considerably higher than this in patients with HMTF. The overall incidence of PTT in patients with HMTF was 30.6% and the rate increased to 50% in 18 patients with CHMTF. At present, it is uncertain whether the increased risk of PTT in patients with HMTF is due to the prolonged gestation or to the more aggressive biological behaviour of abnormal trophoblasts coexisting with a fetus in twin gestation. In our patients with CHMTF, the incidence of developing PTT was unchanged with advancement of gestational age, but maternal prenatal complications were reported to be significantly associated with PTT, as previously reported (Miller et al., 1993
). Despite no increased risk of PTT with continuance of pregnancy, only about one-third had a live outcome (excluding those women who opted to terminate), and pre-eclampsia, intrauterine fetal death and bleeding remain important problems.
In conclusion, our results suggest that patients with HMTF may be allowed to continue the pregnancy, provided that the fetal karyotype is normal and maternal complications can be controlled. However, further clinical assessment of the risks of continuation of pregnancy awaits collection of a larger series of patients with complete cytogenetic data.
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Acknowledgments |
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Notes |
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References |
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Azuma, C., Saji, F., Takemura, M. et al. (1992) Triplet pregnancy involving complete hydatidiform mole and two fetuses: genetic analysis by deoxyribonucleic acid fingerprint. Am. J. Obstet. Gynecol., 166, 664667.[ISI][Medline]
Beischer, N.A. (1961) Hydatidiform mole with coexistent foetus. J. Obstet. Gynaecol. Br. Cwlth, 68, 231237.[ISI]
Block, M.F. and Merrill, J.A. (1982) Hydatidiform mole with coexistent fetus. Obstet. Gynecol., 60, 129134.[ISI][Medline]
Bristow, R.E., Shumway, J.B., Khouzami, A.N. et al. (1996) Complete hydatidiform mole and surviving coexistent twin. Obstet. Gynecol. Surv., 51, 705709.[Medline]
Fisher, R.A., Sheppard, D.M. and Lawler, S.D. (1982) Twin pregnancy with complete hydatidiform mole (46, XX) and fetus (46, XY): genetic origin proved by analysis of chromosome polymorphisms. Br. Med. J., 284, 12181220.[ISI][Medline]
Fishman, D.A., Padilla, L.A., Keh, P. et al. (1998) Management of twin pregnancies consisting of a complete hydatidiform mole and normal fetus. Obstet. Gynecol., 51, 546550.
Garbin, O., Favre, R., Weber, P. et al. (1995) How to deal with a rare entity: the coexistence of a complete mole and a healthy egg in twin pregnancy? Fetal. Diagn. Ther., 10, 337342.[ISI][Medline]
Harada, I., Tsutsumi, O., Takai, Y. et al. (1997) DNA polymorphism analysis of a case of complete hydatidiform mole coexisting with a fetus. Hum. Reprod., 12, 25632566.[Abstract]
Hurteau, J.A., Roth, L.M., Schilder, J.M. et al. (1997) Complete hydatidiform mole coexisting with a twin live fetus: clinical course. Gynecol. Oncol., 66, 156159.[ISI][Medline]
Ishii, J., Iitsuka, Y., Takano, H. et al. (1998) Genetic differentiation of complete hydatidiform moles coexisting with normal fetuses by short tandem repeat (STR)-derived DNA polymorphism analysis. Am. J. Obstet. Gynecol., 179, 628634.[ISI][Medline]
Jauniaux, E. (1998) Ultrasound diagnosis and follow-up of gestational trophoblastic disease. Ultrasound. Obstet. Gynecol., 11, 367377.[ISI][Medline]
Jauniaux, E., Brown, R., Snijders, R.J.M. et al. (1997) Early prenatal diagnosis of triploidy. Am. J. Obstet. Gynecol., 176, 550554.[ISI][Medline]
Jones, W.B. and Lausen, N.H. (1975) Hydatidiform mole with coexistent fetus. Am. J. Obstet. Gynecol., 122, 267272.[ISI][Medline]
Lage, J.M., Mark, S.D., Roberts, D.J. et al. (1992) A flow cytometric study of 137 fresh hydropic placentas: correlation between types of hydatidiform moles and nuclear DNA ploidy. Obstet. Gynecol., 79, 403410.[Abstract]
Matsui, H., Iitsuka, Y., Ishii, J. et al. (1999) Androgenetic complete mole coexistent with a live fetus. Gynecol. Oncol., 74, 217221.[ISI][Medline]
Miller, D., Jackson, R., Ehlen, T. et al. (1993) Complete hydatidiform mole coexistent with a twin live fetus: clinical course of four cases with complete cytogenetic analysis. Gynecol. Oncol., 50, 119123.[ISI][Medline]
Nwosu, E.C., Ferriman, E., McCormack, M.J. et al. (1995) Partial hydatidiform mole and hypertension associated with a live fetus variable presentation in two cases. Hum. Reprod., 10, 24592462.[Abstract]
Ohama, K., Ueda, K., Okamoto, E. et al. (1985) Two cases of dizygotic twins with androgenetic mole and normal conceptus. Hiroshima J. Med. Sci., 34, 371375.[ISI][Medline]
Ohmichi, M., Tasaka, K., Suehar, N. et al. (1986) Hydatidiform mole in a triplet pregnancy following gonadotropin therapy. Acta Obstet. Gynecol. Scand., 65, 523524.[ISI][Medline]
Soysal, M., Kara, S. and Ekici, E. (1996) Twin pregnancy with a fetus and a complete hydatidiform mole. Arch. Gynecol. Obstet., 259, 4144.[ISI][Medline]
Steller, M.A., Genest, D.R., Bernstein, M.R. et al. (1994) Natural history of twin pregnancy with complete hydatidiform mole and coexisting fetus. Obstet. Gynecol., 83, 3542.[Abstract]
Thomas, E.J., Pryce, W.I., Maltby, E.L. et al. (1987) The prospective management of a coexistent hydatidiform mole and fetus. Aust. N. Z. J. Obstet. Gynaecol., 27, 343345.[ISI][Medline]
Vejerslev, L.O. (1991) Clinical management and diagnostic possibilities in hydatidiform mole with coexistent fetus. Obstet. Gynecol. Surv., 46, 577588.[Medline]
Vejerslev, L.O., Dueholm, M. and Nielsen, F.H. (1986) Hydatidiform mole: cytogenetic marker analysis in twin gestation report of two cases. Am. J. Obstet. Gynecol., 155, 614617.[ISI][Medline]
Submitted on August 20, 1999; accepted on November 19, 1999.