Twin Pregnancy With Partial Hydatidiform Mole Biology Essay


Twin pregnancy with mosaic partial hydatidiform mole (PHM) and survival of two healthy fetuses following in vitro fertilization and embryos transfer (IVF-ET) is a rare situation and is considered a challenge for management. A 32-year-old Chinese woman conceived twin pregnancy following IVF-ET. At 22 weeks' gestation, an additional intrauterine echogenic mass with features of PHM were shown by successive ultrasound examinations. At 35 weeks' gestation, two healthy male infants and two placentas were delivered by caesarean section (CS). One male infant had hypospadia and the other one was normal, and both karyotypes of the two healthy babies were 46 XY. Histologic examination of the abnormal placenta confirmed PHM. Genetic study showed the abnormal placental mosaicism (expressed in molar-69XXY and normal vili-46XY), co-existing with a normal diploid new-born (46XY). Serial serum β-hCG levels showed a declining trend and serum β-hCG were undetectable at 6 months after delivery. Our case demonstrated that prolonged gestation with both surviving fetuses was possible by close surveillance of through the entire pregnancy.

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Key Words:Hydatidiform mole · In vitro fertilization · Mosaicism · Partial hydatidiform mole ·Twin pregnancy


Hydatidiform mole (HM) co-existing with a fetus is a rare entity with an estimated incidence of one in 22,000-100,000 pregnancies [Niemann 2007]. Two main types exist on the basis of gross morphological, histological and cytogenetic criteria: complete hydatidiform mole (CHM) co-existing with fetus and partial hydatidiform mole (PHM) co-existing with fetus. The rarity of PHM is not entirely explained, but it is probably because the PHM leads to miscarriage quite early, accounting for an estimated 10-20% early spontaneous abortion. The most common type of PHM with twin pregnancy is that one is a triploid fetus with PHM placenta and the other is a diploid fetus with a diploid placenta. The abnormal fetus with PHM placenta would invariably suffer from serious congenital malformations incompatible with life and usually expires during the first 20-weeks of pregnancy [Matsui 2000]. The increasing proportions of pregnancies conceived following treatment using assisted reproductive technologies are one of the major etiologies for the increasing rates of twin pregnancies with HM [Vaisbuch 2005].

We present the case of survival of dizygotic twins, two fertilized ovum in two sac developed into two healthy male fetus (46XY) following in vitro fertilization and embryos transfer (IVF-ET). The present case conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Human Studies Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Informed consent was obtained from the patient. The extremely rare condition of the dizygotic twins is that the placenta of one single fertilized ovum is mosaicism, composed of two components- the major component is normal tissue (46XY) and the minor is partial hydatidiform mole tissue (69XXY). The twin pregnancy accompanied with PHM was first diagnosed by sonography at 22 weeks' gestation. Observation was continued until survival of two healthy infants at 35 weeks' gestation. To the best of our knowledge, this is the first report of twin pregnancy complicated with mosaic PHM and preeclampsia after IVF-ET, while survival two 46XY male healthy infants.

Case report

The patient was a 32-year-old gravida 4 para 0 who conceived through IVF-ET. The patient experienced 3 years of unexplained infertility after failed IVF-ET twice. Two embryos were transferred to the uterus at 72 hours post egg collection and both embryos survived. Two weeks after the embryo transfer, the result of the patient's urine human chorionic gonadotropin-beta subunit (β-hCG) test was positive. At 17 weeks' gestation, the patient consulted for intermittent vaginal bleeding in Beijing Obstetrics and Gynecology Hospital. Ultrasonographic assessment confirmed the presence of two living fetuses and no evident malformations was observed. At 22 weeks' gestation,two viable fetuses consistent with the age of gestation alongside a normal-looking placenta was observed. In addition, an echogenic mass resembling molar placenta, located at the right posterior uterine wall and very near the unremarkable placenta, was observed. A tentative diagnosis of the twin pregnancy with HM was made at this stage. After realizing the possible associated risks, the patient decided to continue the pregnancy and declined prenatal investigations to establish the fetal karyotypes. The patient was followed up weekly to detect the signs of gestational trophoblastic disease (GTD) and preeclampsia as evidenced by hypertension, proteinuria. In order to assess fetal growth and placental appearance, ultrasound was carried out by the same transonic specialist at two week intervals. The clinical course was unremarkable until the 30th gestational week. The patient presented to the emergency department with complaints of a vaginal watery discharge. Except for vaginal fluid and a positive Actim® PROM test, physical examination revealed no significant findings. Serum β-hCG was 215628 mIU/ml. Ultrasonography showed: (i) a twin pregnancy, with the amnionic membrane separating the amnionic cyst was visible between the twin; (ii) honeycomb construction located in the right anus perineum of anterior placental wall, and the growth of fetus in the same amniotic cavity was less than expected; (iii) the "normal" fetus matched the gestational age and was accompanied by a unremarkable placenta (Figs.1, 2). Normal thyroid function and blood pressure were observed in the absence of proteinuria.

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In the absence of an obvious structural abnormality, with the molar placenta growing slowly if at all and the patient wanting to continue, we adopted a conservative therapy. To inhibit the uterine contraction, the patient was given an intravenous infusion of ritodrine in 5% dextrose at a rate of 100-350μg/min until contractions ceased, with 50μg/min increments every 10 minutes as required (350μg/min maximum). When contractions ceased, the dose was decreased every 30 minutes by 50μg/min steps. This was followed by 10 mg of ritodrine orally for 3 times a day. A course of dexamethasone was given to promote fetal lung maturity: 5 mg intramuscular injection dexamethasone every 12 hours (total 20mg). To prevent infection 400 million units Penicillin in 250 ml of 5% glucose was prescribed and absolute bed rest was suggested. Ultrasound examination and serial measurement of serum β-hCG levels were performed every week. A continuous brown discharge presented for weeks and no obvious amniotic fluid draining was found. The PM placenta did not significantly change, and maternal serum titres of β-hCG within the range of 23654 mIU/ml to 198214 mIU/ml at the period of hospitalization.

Magnesium sulfate was applied to relieve spasms at 33 weeks' gestation, because the patient developed into severe preeclampsia. At 35 weeks' gestation, a low segment transverse CS was performed because of more amnionic fluid leakage and uterine contractions. A 2430 g normal male infant and a 1485 g hypospadia male infant were delivered. Both twins had normal Apgar scores and had uncomplicated neonatal courses. The placenta of 2430g male infant was unremarkable in one chorioamniotic cavity. Details of chorioamniotic cavity with 1485g hypospadia male infant were listed as followed: (â… ) the amnionic fluid was kermesinus and the placenta was measured 24 cm Ã-17 cm Ã-4.5 cm; (â…¡) The placenta was composed of normal tissue and the cystic mole. Approximately 1/3 of placenta appeared to have been invaded and merged by the HM, which measured 7 cm Ã- 17 cm Ã- 3 cm and filled with a diffuse cluster of vesicles of various sizes (0.5-2.0cm); (â…¢) There were two distinct populations of villi identified:large oedematous villi with central cisterns and trophoblast hyperplasia, and small villi that showed some degree of stromal fibrosis (Figs. 3, 4). (â…£) In gross examination, the molar tissue and normal placenta was located in the same chorioamniotic cavity. The umbilical cord was attached in the normal area of the placenta and was contained three blood vessels.

Microscopic examination of the twin placentas revealed that placental disc was dichorionic-diamniotic, with the excess trophoblast focal. At the time of delivery, chromosome analysis using standard cytogenetics and flow cytometry was completed to assess cord blood and amniotic cells. The 2/3 normal placenta tissue karyotypes were 46XY, while the 1/3 molar tissue was triploid 69XXY. From this point of view, the placental mosaicism (expressed in molar-XXY and normal vili-46XY) co-existing with a normal diploid new-born (46XY). The other twin was a diploid fetus with normal placenta (46XY).

On first post-operative day the maternal serum β-hCG level was 53109.10 mIU/ml. The pelvic cavity,chest X-ray were normal. Further measurements of serum β-hCG demonstrated a steady fall and serum β-hCG remained normal (<7 mIU/ml) out to 6 months post delivery. The patient was counseled not to get pregnant for at least 1 year and has remained normal with no sign of recurrence or molar invasion.


Molar pregnancy can be classified on the basis of gross morphological, histological and cytogenetic criteria as either CHM or PHM. Its exact etiology remains unclear. Moglabey YB et al. cited the incidence of PHM varies in ethnic groups, rates vary geographically and reaches 1 in every 250 pregnancies in Eastern Asia [Moglabey 1999]. PHM could also be confused with fertilization of a diploid oocyte with a haploid set of spermatozoa. A twin pregnancy with mosaic PHM and two viable twins after IVF-ET is a rare condition. In our case, the outcome (survival of two fetuses) was excellent compared with that reported previously [Guven ES 2007]. The clinical manifestation of PHM coexistent with fetus is usually a PM with an abnormal triploid fetus. Most patients (73%) with a PM pregnancy present with vaginal bleeding in the late first trimester, with signs and symptoms suggestive of threatened or spontaneous abortion. Triploidy is a highly lethal chromosomal abnormality which causes early spontaneous abortion. The majority of PHM fetuses (93%) that survive are structurally abnormal[Jauniaux E 1998]. Possible maternal complications such as early-onset preeclampsia, hyperthyroidism, and persistent GTD rarely presented in PHM patients. The diagnosis of PM is generally considered only after histologic review of the pathological specimens.

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Some studies advocate that flow cytometry can be used to distinguish a CHM from a PHM, or an early spontaneous abortion with hydropic degeneration from a complete mole [Sánchez-Ferrer ML 2009]. DNA polymorphism analysis to prove paternal origin of molar placenta, and traditional diagnostic methods have been inadequate for accurate diagnosis of classification of HM. The immunohistochemical analysis of the paternally imprinted p57KIP2 gene product can be used to confirm the classification of HM. The positive immunoreactivity of p57KIP2 gene was in accord with PHM. Whereas, in the case of CHM, the immunoreactivity of p57KIP2 gene was absent [Kihara M 2005]. In this case, karyotyping analysis and flow cytometry can be used to confirm mosaic PHM placenta (triploid placenta + diploid placenta). That is, in one cavity of twin pregnancy a diploid fetus resides with the placenta divided into two halves: normal and molar. During the pregnancy, the diagnosis of mosaic and PHM is difficult, and caution must be exercised. Diagnosis of mosaicism can be challenging, since the triploid cells have usually been selected out from the peripheral white blood cells, the starting point for karyotype analysis. Karyotypingflow sorted amniotic cells will aid the diagnosis of mosaicism. In the case described above gross morphological, histological and cytogenetic criteria, that diploid fetus with normal placenta (46XY) attached to a mosaic partial hydatidiform mole placenta(69XXY) in one sac were used.

The recommended treatment and perinatal outcome on hydatidiform mole coexistent with a fetus was reported [Sebire NJ 2002; Ingec M 2006; Kim CH 2008], such as expectant management is preferred instead of pregnancy termination in CHM [ Dolapcioglu K 2009] . While, the expectant treatment of a twin pregnancy with mosaic PHM is little mentioned, for fetal intrauterine growth retardation (IUGR) and fetal distress with premature delivery are likely the outcome. Without obvious fetus abnormity and mosaic PHM limited in little scope placenta, the mother diagnosed with PHM should be managed with expectant management, especially the patient previously infertile suddenly bear with PHM should be carefully selected. It's necessary to careful monitoring of serum β-hCG levels and regular ultrasound. And complete blood count, thyroid function test, C-reactive protein and cervical secretions were also needed to be performed as early as possible in pregnancy. Once serious hemorrhage loses more than menstrual blood volume, active treatment entails termination of pregnancy. Regardless of the methods of termination, overhaul placenta, histopathological analysis and close follow-up with serial β-hCG titers are essential for every patient because of the incidence of malignant diseases. The pathologic presentation of this case was dizygotic twins combined masaic PHM placenta. Histopathological features were the stroma of mosaic PHM in well-preserved villi, which caused one fetus having IUGR and hypospadia in this case.

Due to widespread application of fertility assistant therapy, the incidence of HM after IVF-ET is increasing (Table 1), the management of patients with twin pregnancies companied mosaicism is a rare complication. All reports drawn conclusion that after fully informed, the mothers of twin pregnancies with PHM/CHM have the chances of delivering healthy infant[Piura B 2008; Ko Pc 2007; Hamanoce H 2006; Steigrad SJ 2004; Bovicelli L 2004; Mrntess-de-Oca-valero 1999; Bruchim 2000; Wax 2003; Moini and Riazi 2003]. The exact mechanism of mosaic PHM after IVF-ET is not clear, but there might be an association between blastocyte transfer, the concentrations of inseminating spermatozoa per oocyte, prolonged in vitro culture and the transfer of multiple embryos in PHM patients who had undergone IVF-ET. Huang speculated that higher volume and pressure of culture medium injected into the uterus or the tilt-down position of the patient at the time of ET could be contributory factors for the development of HM [Huang 2007].

In conclusion, early diagnosis will give the opportunity to use conservative management for patients with mosaic PHM following IVF-ET, even when the mole is large. A successful outcome without evidence of malignancy is possible for both of mother and baby. In addition, gynecologists should be aware of the development of HM after IVF-ET and close observation for signs of progression or metastatic gestational trophoblastic disease after delivery is requried.