- Email: [email protected]
Genetically identified complete hydatidiform mole coexisting with a normal fetus following IVF-ET
JOURNAL OF MEDICAL COLLEGES OF PLA Journal of Medical Colleges of PLA 24 (2009) 360–365
www.elsevier.com/locate/jmcpla
Genetically identified complete hydatidiform mole coexisting with a normal fetus following IVF-ET☆ Sui Jianzhong, Sun Xiaofang* Guangzhou Key Laboratory of Reproductive and Genetics, the Third Affiliated Hospital of Guangzhou Medical College, Guangzhou 510150, China Received 19 May 2009; accepted 09 October 2009
Abstract A complete hydatidiform mole coexisting with a fetus following in vitro fertilization and embryo transfer (IVF–ET) is a rare event. The diagnosis is often not easy because of the morphological similarity to a partial mole, but important to the treatment. We present a recent case in which STR polymorphism analysis clearly revealed a different genetic origin for the fetal and molar parts. STR polymorphisms on 15 variable number tandem repeat loci and a gender-determination locus, which were detected by polymerase chain reaction, indicating that the cord/placenta and molar tissue were parental and androgenous, respectively. During follow-up, the patient developed persistent gestational trophoblastic tumor (GTT) which was successfully treated with chemotherapy. In this case, STR polymorphism analysis exactly diagnosed a twin pregnancy consisting of a complete hydatidiform mole and a fetus. Keywords: STR; Complete hydatidiform mole; In vitro fertilization; Twin pregnancy
1. Introduction
chromosomes), and complete hydatidiform mole (CHM), in which the karyotype is diploid (46 chromosomes).
A twin pregnancy coexisting of a complete hydati-
Although a complete mole in a twin pregnancy is rare, it’s
diform mole (CHM) and a fetus is rare, with an
reported that the malignant potential of CHM is higher
incidence of 1 per 22,000–100,000 pregnancies [1].
than that of a partial hydatidiform mole[4]. It is thus
Two types are described[2,3]: partial hydatidiform mole
important to distinguish a complete mole in a twin
(PHM), in which there is a triploid karyotype (69
pregnancy from a partial mole. However, it is difficult and inaccurate to diagnose a complete hydatidiform mole by
☆
Supported by Production and Rresearch Projects of Guangdong
ultrasono-graphy, macroscopic findings and pathological
Province (2007B090400140).
examination, because of the morphological similarity to
* Corresponding author. E-mail address: [email protected](Sun X.)
a partial mole,particularly in cases where coexisting
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
fetus is aborted at an early stage of gestation.
361
IU/L. X-ray examination showed none of lung metastases.
Recently, DNA polymorphism analysis makes it
After counseling with the couple, it was decided to
possible to diagnose a twin molar pregnancy by
terminate the pregnancy. Dilatation and evacuation was
identifying different genetic origins for molar and fetal
performed on the patient at 15 weeks. Macroscopically,
tissue, androgenous for molar tissue and normal
there was a normal female fetus, a normal placenta（Fig. 2）,
biparental for a fetus[5]. In the present paper, we report
and a large molar mass with typical grape-like vesicles
an unusual twin pregnancy with complete H-mole and a
measured 152 mm×75 mm×148 mm (Fig. 3). Pathologic
coexisting fetus following IVF–ET diagnosed by STR
examination showed a complete hydatidiform mole
polymorphism analysis. This woman was evacuated at
coexisting with a normal fetus (Fig. 4).
15 weeks of gestation. However, about one month after delivery, she developed a persistent GTT that required Etoposide (VP-16) –diamminedichloroplatinum (DDP) chemotherapy to achieve complete remission.
2. Case report A 33-year-old Chinese woman, gravida 2, parous 0, with one previous spontaneous abortion, had undergone
Fig. 1. Ultrasonography of complete hydatidiform mole and
in vitro fertilization and embryo transfer (IVF–ET), and
surviving coexistent at 15 weeks of gestation.
transferred two embryos in the uterus. Five weeks later, a positive fetal heart and a poorly defined sac was outlined, identified on transvaginal ultrasound. At 9 weeks
the
patient
had
another
ultrasonographic
examination because of vaginal bleeding, that revealed a living fetus with normal fetal heart beat; however, there was a subchorionic echogenic lesion sized by 113 mm×52 mm. She was thought to be at risk of threatened abortion, and advised to have absolute bed rest and close
Fig. 2. The delivered fetus with normal placenta.
follow-up. At the 15th week of gestation, the patient complained of sustained vaginal bleeding, abdominal pain, and vomiting. An ultrasound scan showed a normal fetus of the 15th week of gestation coexisted with a suspicious subchorionic hematoma sized 95 mm×115 mm×28 mm, and a very large cystic mass measured 150 mm×76 mm×146 mm (Fig. 1), all of which was consistent with CHM. The serum level of human chorionic gonadotrophins (hCG) was >1000000
Fig.3. Molar tissue with obvious grape-like pattern.
362
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
Fig. 4. Complete hydatidiform mole. Villi have extensive stromal edema with central cistern and a circumferential proliferation of trophoblast.
Fig.5A, Fig.5B: DNA fingerprinting of parents and mole. Fig.5C: DNA fingerprinting of fetus. Table 1 Genotypes of the parents, fetus and molar tissue Sample
Father
information
Mother
Fetus
Mole
Origin
D8S1179
10
14
10
12
10
14
10
10
D21S11
29
31
29
33.2
29
31
31
31
D7S820
10
10
10
12
10
10
10
10
CSF1PO
12
12
9
12
9
12
12
12
D3S1358
17
17
17
18
17
17
17
17
TH01
7
9
6
9
6
7
7
7
*, #
D13S317
10
12
8
10
10
10
12
12
#
D16S539
12
13
11
11
11
12
13
13
*, #
D2S1338
21
24
18
20
18
24
24
24
*, #
D19S433
13
14.2
15.2
16.2
13
16.2
14.2
14.2
*, #
vWA
14
17
17
18
14
17
14
14
#
TPOX
8
11
11
11
8
11
11
11
D18S51
14
15
14
16
14
15
15
15
AMEL
X
Y
X
X
X
X
X
X
D5S818
8
11
11
11
11
11
8
8
#
FGA
23
23
22
24
23
24
23
23
*, #
Fetal DNA showed bi-parental origin (*) and molar DNA showed paternal origin (#).
#
#
363
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
In addition to the pathological examination, STR-
3. Discussion
derived DNA polymorphism analysis clarified the paternity of the fetus and molar tissue (Fig.5A, Fig.5B,
We can analyze the mechanisms of hydatidiform
Fig.5C). Genomic DNA extracted from the fetus, molar
mole (HM) by molecular methods[6], with it divided
tissue and parental peripheral blood leukocytes was
into complete and partial hydatidiform mole. The most
amplified with 15 variable number tandem repeat loci
usual mechanism of CHM is the fusion of a spermatic
and a gender-determination marker using a commer-
haploid genome and an empty ovocyte (i.e., one in
cially released kit for personal identification (Amp
which the egg nucleus is absent or inactivated),
FISTR Identifiler Kit, Applied Biosystems, USA) (Table
followed by duplication of the spermatic haploid
1). DNA was amplified under the following conditions:
genome to obtain 46 chromosomes. The chromosomes
polymerase activation at 95℃ for 11 min, followed by
of each pair are identical; the mole is said to be
28 cycles of 1 min at 94℃, 1 min at 59℃, 1 min at
homozygous and the karyotype is always 46,XX. The
72℃ and extension for 60 min at 60℃. A Genetic
second mechanism, an empty egg is fertilized by two
Analyzer 3100 was used for fragment analysis and the
sperm. In this case the mole is said to be heterozygous
data were further analyzed using Genescan 3.1 and
and the karyotype can be either 46,XX or 46,XY[7].
Genotyper 2.0 software (Applied Biosystems, CA,
Partial moles derive from dispermic fertilization of a
USA). The 15 polymorphic STR loci were examined
haploid normal oocyte and produce a triploid set of
and 10 were found to be informative. There were 5 loci
chromosomes.
of fetus DNA showed biparental alleles and was
The use of ovulation-inducing drugs such as
confirmed as biparental in origin (Table 1,*). Molar
clomiphene citrate or gonadotrophin (HMG or FSH)
DNA is all of paternal origin. In addition, all molar
has raised the concern that these women may be at
alleles were homozygous. This result confirmed that the
increased risk of cancer. It is expected that, with the
molar tissue derived from monospermic androgenesis
increase in the utilization of ovulation induction
(Table 1, #). The STR results confirmed that this was a
therapy, the rate of multiple gestations containing
case of a complete hydatidiform mole coexisting with a
hydatidiform mole will rise, and the overall risk of
fetus.
developing persistent GTT may be increased[8]. In
Postoperatively, serum ß-hCG level showed a
addition, the risk of developing persistent GTT in CHM
steady fall. However, about one month after delivery,
is higher (12–20%) than in partial mole (4%) [9,10].
when the patient revisited, and at that time we found
Although
the level of ß-hCG was still high, up to 14335 IU/L. We
coexisting with a fetus following IVF-ET developed
suspected persistent gestational trophoblastic tumor
into persistent GTT, which was the case in our patient.
(GTT), and decided to administer one cycle of
It is important to distinguish between complete and
Etoposide (VP-16)- diamminedichloroplatinum（DDP)
partial moles because the malignant potential is four
chemotherapy. Chest X-ray found that pulmonary
times higher in patients with a complete hydatidiform
metastasis was normal. Four cycles after Etoposide
mole than in patients with a partial hydatidiform
(VP-16)- diamminedichloroplatinum（DDP) chemo-
mole[11]. Further more, although a triploid fetus in a
therapy, ß-hCG level was normalized, and no further
partial hydatidiform mole has no chance of survival, a
problems followed.
fetus coexisting with a complete hydatidiform mole in a
rare,
a
complete
hydatidiform
mole
364
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
twin pregnancy may survive[12].
TH01, D13S317, D16S539, D2S1338, D19S433, vWA,
It was reported that STR-derived DNA polymorphism
TPOX, D18S51, D5S818, FGA, and the Amel locus on
analysis was a useful and accurate molecular method to
chromosomes X and Y) and represents the largest
diagnose CHM[13]. In this case, 15 variable number
number of such validated cases. The high number of
tandem repeat loci and a gender–determination locus
loci tested simultaneously saved time and was helpful
were used, and the result showed that fetal DNA was
in cases with partial allelic profiles secondary to DNA
biparental in origin, but molar DNA was all of paternal
degradation.
origin, indicating that this case was twin pregnancy. The
As we all know, conventional diagnostic methods
molar DNA confirmed as monospermic androgenesis and
including ultrasonography, macroscopic findings and
DNA ploidy analysis of molar tissue showed diploid
pathological examination were inadequate for accurate
karyotype (46, XX), typical of a CHM. These findings
diagnosis of hydatidiform mole, even when these
confirmed that this molar tissue was derived from a
measures
CHM. Inversely, the fetal DNA was biparental, and
polymorphism analysis is a fast, convenient and
DNA ploidy was also diploid type (46, XX). These
accurate molecular method, could be used for the
findings suggested that it was a normal fetus. Thus, this
diagnosis of hydatidiform mole, especially for CHM
case was finally diagnosed as twin pregnancy with
with a co-existing fetus, and become a standard
CHM coexisting with a normal fetus following IVF-ET.
diagnostic method.
Although
the
natural
clinical
course
were
combined.
STR-derived
DNA
and
appropriate management of twin pregnancy with
References
complete hydatidiform mole and a coexisting fetus are limited due to the rarity of this phenomenon, in the
1.
cases which received treatment for infertility, like the present case, the termination of pregnancy should be
Jones WB, Lauersen NH. Hydatidiform mole with coexistent fetus. Am J Obstet Gynecol 1975; 122(3): 267.
2.
Niikawa N, Merotto E, Kajii T. Origin of acrocentric
decided very carefully considering the patient’s wants,
trisomies in spontaneous abortuses. Hum Genet 1977;
clinical status, and laboratory findings. It has been
40(1): 73.
suggested that serially decreasing serum ß-hCG levels
3.
Vassilakos P, Riotton G, Kajii T. Hydatidiform mole: two
and normal fetal karyotype without any serious clinical
entities. A morphologic and cytogenetic study with some
complications
clinical consideration. Am J Obstet Gynecol 1977;
are
requirements
for
expectant
management[14,15]. Also, it might be necessary to follow up the patients carefully for possible progression
127(2): 167. 4.
Goldstein DP, Berkowitz RS. Current management of
of persistent or metastatic GTT after termination,
complete and partial molar pregnancy. J Reprod Med
because the risk of progression is high in these cases.
1994; 39(3): 139.
It is worth mentioning that DNA microsatellite
5.
Marcorelles P, Audrezet MP, Le Bris MJ, et al. Diagnosis
polymorphism has been used to resolve diagnostic
and outcome of complete hydatidiform mole coexisting
dilemmas centered on hydatidiform mole（HM）in our
with a live twin fetus. Eur J Obstet Gynecol Reprod Biol
laboratory, this study applied a commercially available
2005; 118(1): 21.
kit, PowerPlex16, that simultaneously tests 16 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358,
6.
Ishii J, Iitsuka Y, Takano H, et al. Genetic differentiation of complete hydatidiform moles coexisting with normal
365
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
fetuses by short tandem repeat-derived deoxyribonucleic
postmolar trophoblastic disease after partial molar
acid polymorphism analysis. Am J Obstet Gynecol 1998;
pregnancy. Gynecol Oncol 1993; 48(2): 165.
179(3 pt 1): 628. 7.
Vuong PN, Guillet JL, Houissa-Vuong S, et al. Pathology
possibilities in hydatidiform mole with coexistent fetus.
of gestational trophoblastic tumors. Gynecol Obstet
Obstet Gynecol Surv 1991; 46(9): 577.
Fertil 2000; 28(12): 913. 8.
9.
12. Vejerslev LO. Clinical management and diagnostic
13. Wax JR, Pinette MG, Chard R, et al. Prenatal diagnosis
Petignat P, Vassilakos P, Campana A. Are fertility drugs a
by DNA polymorphism analysis of complete mole with
risk factor for persistent trophoblastic tumour? Hum
coexisting twin. Am J Obstet Gynecol 2003; 188(4):
Reprod 2002;17(6): 1610.
1105.
Steller MA, Genest DR, Bernstein MR, et al. Clinical
14. Suzuki M, Matsunobu A, Wakita K, et al. Hydatidiform
features of multiple conception with partial or complete
mole with a surviving coexisting fetus. Obstet Gynecol
molar pregnancy and coexisting fetuses. J Reprod Med
1980; 56(3):384–388.
1994; 39(3): 147. 10. Bristow RE, Shumway JB, Khouzami AN, et al. Complete hydatidiform mole and surviving coexistent
15. Thomas EJ, Pryce WI, Matlby EL, et al. The prospective management of a coexistent hydatidiform mole and fetus. Aust NZ J Obstet Gynecol 1987; 27(4):343.
twin. Obstet Gynecol Surv 1996; 51(12): 705. 11. Goto S, Yamada A, Ishizuka T, et al. Development of
(Editor Lu Renmin)
www.elsevier.com/locate/jmcpla
Genetically identified complete hydatidiform mole coexisting with a normal fetus following IVF-ET☆ Sui Jianzhong, Sun Xiaofang* Guangzhou Key Laboratory of Reproductive and Genetics, the Third Affiliated Hospital of Guangzhou Medical College, Guangzhou 510150, China Received 19 May 2009; accepted 09 October 2009
Abstract A complete hydatidiform mole coexisting with a fetus following in vitro fertilization and embryo transfer (IVF–ET) is a rare event. The diagnosis is often not easy because of the morphological similarity to a partial mole, but important to the treatment. We present a recent case in which STR polymorphism analysis clearly revealed a different genetic origin for the fetal and molar parts. STR polymorphisms on 15 variable number tandem repeat loci and a gender-determination locus, which were detected by polymerase chain reaction, indicating that the cord/placenta and molar tissue were parental and androgenous, respectively. During follow-up, the patient developed persistent gestational trophoblastic tumor (GTT) which was successfully treated with chemotherapy. In this case, STR polymorphism analysis exactly diagnosed a twin pregnancy consisting of a complete hydatidiform mole and a fetus. Keywords: STR; Complete hydatidiform mole; In vitro fertilization; Twin pregnancy
1. Introduction
chromosomes), and complete hydatidiform mole (CHM), in which the karyotype is diploid (46 chromosomes).
A twin pregnancy coexisting of a complete hydati-
Although a complete mole in a twin pregnancy is rare, it’s
diform mole (CHM) and a fetus is rare, with an
reported that the malignant potential of CHM is higher
incidence of 1 per 22,000–100,000 pregnancies [1].
than that of a partial hydatidiform mole[4]. It is thus
Two types are described[2,3]: partial hydatidiform mole
important to distinguish a complete mole in a twin
(PHM), in which there is a triploid karyotype (69
pregnancy from a partial mole. However, it is difficult and inaccurate to diagnose a complete hydatidiform mole by
☆
Supported by Production and Rresearch Projects of Guangdong
ultrasono-graphy, macroscopic findings and pathological
Province (2007B090400140).
examination, because of the morphological similarity to
* Corresponding author. E-mail address: [email protected](Sun X.)
a partial mole,particularly in cases where coexisting
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
fetus is aborted at an early stage of gestation.
361
IU/L. X-ray examination showed none of lung metastases.
Recently, DNA polymorphism analysis makes it
After counseling with the couple, it was decided to
possible to diagnose a twin molar pregnancy by
terminate the pregnancy. Dilatation and evacuation was
identifying different genetic origins for molar and fetal
performed on the patient at 15 weeks. Macroscopically,
tissue, androgenous for molar tissue and normal
there was a normal female fetus, a normal placenta（Fig. 2）,
biparental for a fetus[5]. In the present paper, we report
and a large molar mass with typical grape-like vesicles
an unusual twin pregnancy with complete H-mole and a
measured 152 mm×75 mm×148 mm (Fig. 3). Pathologic
coexisting fetus following IVF–ET diagnosed by STR
examination showed a complete hydatidiform mole
polymorphism analysis. This woman was evacuated at
coexisting with a normal fetus (Fig. 4).
15 weeks of gestation. However, about one month after delivery, she developed a persistent GTT that required Etoposide (VP-16) –diamminedichloroplatinum (DDP) chemotherapy to achieve complete remission.
2. Case report A 33-year-old Chinese woman, gravida 2, parous 0, with one previous spontaneous abortion, had undergone
Fig. 1. Ultrasonography of complete hydatidiform mole and
in vitro fertilization and embryo transfer (IVF–ET), and
surviving coexistent at 15 weeks of gestation.
transferred two embryos in the uterus. Five weeks later, a positive fetal heart and a poorly defined sac was outlined, identified on transvaginal ultrasound. At 9 weeks
the
patient
had
another
ultrasonographic
examination because of vaginal bleeding, that revealed a living fetus with normal fetal heart beat; however, there was a subchorionic echogenic lesion sized by 113 mm×52 mm. She was thought to be at risk of threatened abortion, and advised to have absolute bed rest and close
Fig. 2. The delivered fetus with normal placenta.
follow-up. At the 15th week of gestation, the patient complained of sustained vaginal bleeding, abdominal pain, and vomiting. An ultrasound scan showed a normal fetus of the 15th week of gestation coexisted with a suspicious subchorionic hematoma sized 95 mm×115 mm×28 mm, and a very large cystic mass measured 150 mm×76 mm×146 mm (Fig. 1), all of which was consistent with CHM. The serum level of human chorionic gonadotrophins (hCG) was >1000000
Fig.3. Molar tissue with obvious grape-like pattern.
362
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
Fig. 4. Complete hydatidiform mole. Villi have extensive stromal edema with central cistern and a circumferential proliferation of trophoblast.
Fig.5A, Fig.5B: DNA fingerprinting of parents and mole. Fig.5C: DNA fingerprinting of fetus. Table 1 Genotypes of the parents, fetus and molar tissue Sample
Father
information
Mother
Fetus
Mole
Origin
D8S1179
10
14
10
12
10
14
10
10
D21S11
29
31
29
33.2
29
31
31
31
D7S820
10
10
10
12
10
10
10
10
CSF1PO
12
12
9
12
9
12
12
12
D3S1358
17
17
17
18
17
17
17
17
TH01
7
9
6
9
6
7
7
7
*, #
D13S317
10
12
8
10
10
10
12
12
#
D16S539
12
13
11
11
11
12
13
13
*, #
D2S1338
21
24
18
20
18
24
24
24
*, #
D19S433
13
14.2
15.2
16.2
13
16.2
14.2
14.2
*, #
vWA
14
17
17
18
14
17
14
14
#
TPOX
8
11
11
11
8
11
11
11
D18S51
14
15
14
16
14
15
15
15
AMEL
X
Y
X
X
X
X
X
X
D5S818
8
11
11
11
11
11
8
8
#
FGA
23
23
22
24
23
24
23
23
*, #
Fetal DNA showed bi-parental origin (*) and molar DNA showed paternal origin (#).
#
#
363
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
In addition to the pathological examination, STR-
3. Discussion
derived DNA polymorphism analysis clarified the paternity of the fetus and molar tissue (Fig.5A, Fig.5B,
We can analyze the mechanisms of hydatidiform
Fig.5C). Genomic DNA extracted from the fetus, molar
mole (HM) by molecular methods[6], with it divided
tissue and parental peripheral blood leukocytes was
into complete and partial hydatidiform mole. The most
amplified with 15 variable number tandem repeat loci
usual mechanism of CHM is the fusion of a spermatic
and a gender-determination marker using a commer-
haploid genome and an empty ovocyte (i.e., one in
cially released kit for personal identification (Amp
which the egg nucleus is absent or inactivated),
FISTR Identifiler Kit, Applied Biosystems, USA) (Table
followed by duplication of the spermatic haploid
1). DNA was amplified under the following conditions:
genome to obtain 46 chromosomes. The chromosomes
polymerase activation at 95℃ for 11 min, followed by
of each pair are identical; the mole is said to be
28 cycles of 1 min at 94℃, 1 min at 59℃, 1 min at
homozygous and the karyotype is always 46,XX. The
72℃ and extension for 60 min at 60℃. A Genetic
second mechanism, an empty egg is fertilized by two
Analyzer 3100 was used for fragment analysis and the
sperm. In this case the mole is said to be heterozygous
data were further analyzed using Genescan 3.1 and
and the karyotype can be either 46,XX or 46,XY[7].
Genotyper 2.0 software (Applied Biosystems, CA,
Partial moles derive from dispermic fertilization of a
USA). The 15 polymorphic STR loci were examined
haploid normal oocyte and produce a triploid set of
and 10 were found to be informative. There were 5 loci
chromosomes.
of fetus DNA showed biparental alleles and was
The use of ovulation-inducing drugs such as
confirmed as biparental in origin (Table 1,*). Molar
clomiphene citrate or gonadotrophin (HMG or FSH)
DNA is all of paternal origin. In addition, all molar
has raised the concern that these women may be at
alleles were homozygous. This result confirmed that the
increased risk of cancer. It is expected that, with the
molar tissue derived from monospermic androgenesis
increase in the utilization of ovulation induction
(Table 1, #). The STR results confirmed that this was a
therapy, the rate of multiple gestations containing
case of a complete hydatidiform mole coexisting with a
hydatidiform mole will rise, and the overall risk of
fetus.
developing persistent GTT may be increased[8]. In
Postoperatively, serum ß-hCG level showed a
addition, the risk of developing persistent GTT in CHM
steady fall. However, about one month after delivery,
is higher (12–20%) than in partial mole (4%) [9,10].
when the patient revisited, and at that time we found
Although
the level of ß-hCG was still high, up to 14335 IU/L. We
coexisting with a fetus following IVF-ET developed
suspected persistent gestational trophoblastic tumor
into persistent GTT, which was the case in our patient.
(GTT), and decided to administer one cycle of
It is important to distinguish between complete and
Etoposide (VP-16)- diamminedichloroplatinum（DDP)
partial moles because the malignant potential is four
chemotherapy. Chest X-ray found that pulmonary
times higher in patients with a complete hydatidiform
metastasis was normal. Four cycles after Etoposide
mole than in patients with a partial hydatidiform
(VP-16)- diamminedichloroplatinum（DDP) chemo-
mole[11]. Further more, although a triploid fetus in a
therapy, ß-hCG level was normalized, and no further
partial hydatidiform mole has no chance of survival, a
problems followed.
fetus coexisting with a complete hydatidiform mole in a
rare,
a
complete
hydatidiform
mole
364
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
twin pregnancy may survive[12].
TH01, D13S317, D16S539, D2S1338, D19S433, vWA,
It was reported that STR-derived DNA polymorphism
TPOX, D18S51, D5S818, FGA, and the Amel locus on
analysis was a useful and accurate molecular method to
chromosomes X and Y) and represents the largest
diagnose CHM[13]. In this case, 15 variable number
number of such validated cases. The high number of
tandem repeat loci and a gender–determination locus
loci tested simultaneously saved time and was helpful
were used, and the result showed that fetal DNA was
in cases with partial allelic profiles secondary to DNA
biparental in origin, but molar DNA was all of paternal
degradation.
origin, indicating that this case was twin pregnancy. The
As we all know, conventional diagnostic methods
molar DNA confirmed as monospermic androgenesis and
including ultrasonography, macroscopic findings and
DNA ploidy analysis of molar tissue showed diploid
pathological examination were inadequate for accurate
karyotype (46, XX), typical of a CHM. These findings
diagnosis of hydatidiform mole, even when these
confirmed that this molar tissue was derived from a
measures
CHM. Inversely, the fetal DNA was biparental, and
polymorphism analysis is a fast, convenient and
DNA ploidy was also diploid type (46, XX). These
accurate molecular method, could be used for the
findings suggested that it was a normal fetus. Thus, this
diagnosis of hydatidiform mole, especially for CHM
case was finally diagnosed as twin pregnancy with
with a co-existing fetus, and become a standard
CHM coexisting with a normal fetus following IVF-ET.
diagnostic method.
Although
the
natural
clinical
course
were
combined.
STR-derived
DNA
and
appropriate management of twin pregnancy with
References
complete hydatidiform mole and a coexisting fetus are limited due to the rarity of this phenomenon, in the
1.
cases which received treatment for infertility, like the present case, the termination of pregnancy should be
Jones WB, Lauersen NH. Hydatidiform mole with coexistent fetus. Am J Obstet Gynecol 1975; 122(3): 267.
2.
Niikawa N, Merotto E, Kajii T. Origin of acrocentric
decided very carefully considering the patient’s wants,
trisomies in spontaneous abortuses. Hum Genet 1977;
clinical status, and laboratory findings. It has been
40(1): 73.
suggested that serially decreasing serum ß-hCG levels
3.
Vassilakos P, Riotton G, Kajii T. Hydatidiform mole: two
and normal fetal karyotype without any serious clinical
entities. A morphologic and cytogenetic study with some
complications
clinical consideration. Am J Obstet Gynecol 1977;
are
requirements
for
expectant
management[14,15]. Also, it might be necessary to follow up the patients carefully for possible progression
127(2): 167. 4.
Goldstein DP, Berkowitz RS. Current management of
of persistent or metastatic GTT after termination,
complete and partial molar pregnancy. J Reprod Med
because the risk of progression is high in these cases.
1994; 39(3): 139.
It is worth mentioning that DNA microsatellite
5.
Marcorelles P, Audrezet MP, Le Bris MJ, et al. Diagnosis
polymorphism has been used to resolve diagnostic
and outcome of complete hydatidiform mole coexisting
dilemmas centered on hydatidiform mole（HM）in our
with a live twin fetus. Eur J Obstet Gynecol Reprod Biol
laboratory, this study applied a commercially available
2005; 118(1): 21.
kit, PowerPlex16, that simultaneously tests 16 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358,
6.
Ishii J, Iitsuka Y, Takano H, et al. Genetic differentiation of complete hydatidiform moles coexisting with normal
365
Sui Jianzhong et al. / Journal of Medical Colleges of PLA 24 (2009) 360–365
fetuses by short tandem repeat-derived deoxyribonucleic
postmolar trophoblastic disease after partial molar
acid polymorphism analysis. Am J Obstet Gynecol 1998;
pregnancy. Gynecol Oncol 1993; 48(2): 165.
179(3 pt 1): 628. 7.
Vuong PN, Guillet JL, Houissa-Vuong S, et al. Pathology
possibilities in hydatidiform mole with coexistent fetus.
of gestational trophoblastic tumors. Gynecol Obstet
Obstet Gynecol Surv 1991; 46(9): 577.
Fertil 2000; 28(12): 913. 8.
9.
12. Vejerslev LO. Clinical management and diagnostic
13. Wax JR, Pinette MG, Chard R, et al. Prenatal diagnosis
Petignat P, Vassilakos P, Campana A. Are fertility drugs a
by DNA polymorphism analysis of complete mole with
risk factor for persistent trophoblastic tumour? Hum
coexisting twin. Am J Obstet Gynecol 2003; 188(4):
Reprod 2002;17(6): 1610.
1105.
Steller MA, Genest DR, Bernstein MR, et al. Clinical
14. Suzuki M, Matsunobu A, Wakita K, et al. Hydatidiform
features of multiple conception with partial or complete
mole with a surviving coexisting fetus. Obstet Gynecol
molar pregnancy and coexisting fetuses. J Reprod Med
1980; 56(3):384–388.
1994; 39(3): 147. 10. Bristow RE, Shumway JB, Khouzami AN, et al. Complete hydatidiform mole and surviving coexistent
15. Thomas EJ, Pryce WI, Matlby EL, et al. The prospective management of a coexistent hydatidiform mole and fetus. Aust NZ J Obstet Gynecol 1987; 27(4):343.
twin. Obstet Gynecol Surv 1996; 51(12): 705. 11. Goto S, Yamada A, Ishizuka T, et al. Development of
(Editor Lu Renmin)