Familial recurrent molar pregnancy: a case report (2004)

Gestational trophoblastic disease (GTD) is a manifestation of an aberrant fertilization event that leads to a proliferative process and potentially to an invasive neoplasm. The hydatidiform mole is the most common form of GTD (80% of cases) (1). Hydatidiform mole is a benign trophoblastic neoplasm characterized by an abnormal development of the embryo and proliferation of placental villi (2). The risk factors identified for molar pregnancy are maternal age >35 or <20 years, history of previous molar pregnancy, pasthistory of abortions, recurrent abortions and blood group ‘A’. Progression to gestational trophoblastic tumor has been found in 3% patients with molar pregnancy (3). The genetic and familial trend of molar pregnancy has long been suspected and postulated. Here we present a rare case of recurrent mole with a family history of molar pregnancy. A 43-year-old woman was admitted to the gynecologic ward of the Post Graduate Institute of Medical Education and Research, Chandigarh, India, with amenorrhea of 11 weeks and bleeding per vaginam on-and-off since conception. She was a fifth gravida with history of four previous molar pregnancies. In her family history, she had one elder sister and one younger sister. The elder sister had one term stillbirth followed by two molar pregnancies. Her younger sister had one molar pregnancy. There was no history of consanguineous marriage in her or in her sisters. Her general physical examination revealed no abnormality. Her blood pressure was 120/80 mmHg and she was not anemic. Her blood group was ‘B’ Rh positive. On pelvic examination the uterus was soft and enlarged to 14–16 weeks' size. The internal os was closed and there was minimal bleeding through the cervix. There was no adnexal mass. Her urine pregnancy test was positive at 1 : 100 dilutions and negative at 1 : 1000 dilutions (test used = Pregcolor tube test, INFAR India Ltd; sensitivity 200 IU/l) The ultrasound examination was suggestive of molar pregnancy because of the uniform snowstorm appearance in the uterine cavity and absence of fetal parts. This patient was admitted and suction evacuation was carried out. Histopathology of the products confirmed hydatidiform mole. Recurrent GTD is a rare phenomenon and has been reported in only 0.6–2.6% of subsequent pregnancies (4). It has significant clinicopathological implications, which include risk of malignant sequelae and subsequent poor reproductive performance. This case has been reported because of two rare clinical situations, i.e. recurrence of GTD in this patient as well as family history of recurrent mole. In addition there is a need to know the prognosis, regarding future obstetric outcome in these patients with such a scenario. Hydatidiform mole arises from an ovum that has undergone fertilization by a haploid sperm that duplicated its own chromosomes after meiosis. The chromosomes of the ovum are either absent or inactivated. Thus it is paternal in origin. Recent data have provided molecular evidence to suggest that familial recurrent moles are diploid, biparental and arise from independent conceptions. A narrowing of the gene interval on chromosome 19q13.3–13.4 is suggested by haplotype analysis in two sisters with similar history (5). In a study carried out by Moglabey et al. (2), women with recurrent hydatidiform mole are homozygous for a rare autosomal recessive gene. A higher incidence of subsequent molar pregnancies has been reported to occur with in vitro fertilization (IVF), which may be because of a predisposition for abnormal fertilization leading to triploid embryos. The use ofintracytoplasmic sperm injection (ICSI) may reduce the incidence of this malformation (6). A familial hydatidiform mole syndrome has been described in the literature. Recent data have suggested that it is an autosomal recessive trait. Also a higher incidence of recurrent familial mole was seen with extensive intermarriage, suggesting a defect in HLA histocompatibility (7). Familial recurrent molar pregnancies are exceedingly rare. A family with three recurrent moles in one sister and five in the other has been reported (7). However both these sisters were married to first-degree cousins. In the present case, with five recurrent molar pregnancies, there was no history of consanguinity in her or any of her two sisters who also had two and one molar pregnancies, respectively. The incidence of postmolar tumor has been reported to be 18–29% in the USA and 8–10% in western Europe, with higher risk observed in women older than 40. Patients with repetitive molar pregnancy are at increased risk of developing persistent tumor in their later episodes of molar gestation (8). This was noted to the extent of 50% after the second molar pregnancy as compared to a rate of 22% after first mole (9). Of the subsequent pregnancies in patients with hydatidiform mole, fullterm delivery, spontaneous abortions and recurrent mole occurred in 55.6%, 27.8% and 16.7%, respectively (10). However, following two episodes of molar pregnancy, repeat mole occurred in 23.1% women and fullterm deliveries were seen in 53.8% (9). According to Lorigan PC et al. (11), risk of second mole is less than 1% in the UK, with a trend towards increased incidence in Indian and Pakistani women (relative risk 2.4). So women with two episodes of molar pregnancy, although having a higher risk of another mole as well as postmolar tumor, still have a greater than 50% chance of a normal subsequent pregnancy. Lastly, the future obstetric management of this woman needs to be discussed. In women with molar pregnancy, the recommendation for any subsequent pregnancy is to have a pelvic ultrasonogram during the first trimester to confirm normal gestational development. This option alone is not enough for our case, who has already undergone five molar pregnancies. The possibility of ICSI can be considered in this case, as it has been reported to decrease the chances of molar pregnancy (12). However it remains to be seen how much benefit can be obtained by this intervention, as the pathogenesis of familial recurrent mole is different from a sporadic molar event. Intracytoplasmic sperm injection followed by preimplantation genetic diagnosis is a therapeutic option to exclude complete mole arising from dispermic fertilization. If 46 XX embryos are also excluded, moles resulting from duplication of haploid X-bearing spermatozoan will be prevented. But in cases of familial recurrent mole where the conceptions are diploid, biparental (5) and may result from a defective maternal gene (2) and oocyte defect predisposing to abnormal fertilization, donor oocyte IVF would be another alternative (6).